Biological Differences Between Ovarian Cancer-associated Fibroblasts and Contralateral Normal Ovary-derived Mesenchymal Stem Cells

Background/Aim: The aim of this study was to clarify the biological differences between ovarian cancerassociated fibroblasts (OCa-CAFs) and normal ovary-derived mesenchymal stem cells (NO-MSCs). Materials and Methods: Surgically resected ovarian cancer and contralateral normal ovarian tissue samples were cut into small pieces for culture as “explants”. The number of outgrown cells, their proliferative kinetics, and expression levels of cell surface markers of CAFs, as well as three miRNAs in OCa-CAFs and NO-MSCs were compared directly. Differentially expressed genes between both groups were also investigated. Results: Comparable numbers of outgrown cells were harvested from both groups. Significantly higher expression of α-smooth muscle actin and miR-142 was found in OCa-CAFs, which decreased significantly during ex vivo cell expansion. A total of 21 differentially expressed genes were identified between both groups. Conclusion: OCa-CAFs showed different biological properties in direct comparison with NO-MSCs, which might play major roles in the pathogenesis of ovarian cancer

A case of chorioangioma with polyhydramnios

Chorioangioma is the most common benign placental tumor arising from the chorionic stroma and capillaries, and histologically accounts for about 1% of placental tumors1). It rarely exceeds 5 cm in diameter, and is clinically diagnosed in 1 out of every 8,000-50,000 patients1). We report a patient with a relatively large chorioangioma (10 cm in diameter) accompanied by polyhydramnios

Histological and Immunohistochemical Analysis of Fetal Hypoplastic Lungs: Preliminary Study

To investigate cellular growth and differentiation of the airway epithelium of the human fetal lung using immunohistochemistry, with a particular focus on cases of pulmonary hypoplasia. A total of 25 autopsy cases of stillbirth and early neonatal death were examined at Nagasaki University Hospital from 1986 to 1997. Using immunohistochemistry, we determined the expression of a variety of growth factors (EGFR, HGFR, GRP and SAPA) in lung tissues with or without pulmonary hypoplasia. A significant decrease in radial alveolar count was detected in hypoplastic lungs compared with normal lungs. The expressions of EGFR, HGFR and GRP in tissues from hypoplastic lungs were significantly lower than in tissues from normal lungs, but the expression of SAPA was not different between the two groups. Our results indicated that significant abnormalities of cellular growth and differentiation are present in pulmonary hypoplasia. However, lung maturation in pulmonary hypoplasia was not significantly different to that in normal lungs

Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer.

OBJECTIVES: The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. METHODS: Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. RESULTS: Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. CONCLUSIONS: These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment

A case of placenta previa accreta successfully treated by open infrarenal aortic clamping

Open infrarenal aortic clamping has been performed for traumatic pelvic hemorrhage or aortic rupture, and there are few reports of its use in the field of obstetrics and gynecology1). We report a patient with placenta previa accreta who was successfully treated by open infrarenal aortic clamping

AMH Concentrations in Peritoneal Fluids of Women With and Without Endometriosis

Background: As its name indicates, anti-Mullerian hormone (AMH) is primarily found as an inhibitor of the Mullerian duct in male fetus. On the other hand, AMH may act as a mediator of Mullerian duct-derived female tissue, such as endometrium in normal and pathological conditions. However, the role of AMH in the functional regulations of endometriosis is not well understood. It can be hypothesized that AMH in peritoneal fluids may affect the activity of peritoneal endometriosis. In this study, we investigated the levels of AMH in peritoneal fluids (PF) in women with and without endometriosis. Methods: PF were collected during laparoscopy from 90 women diagnosed as having advanced endometriosis (rASRM stage III, n = 30; stage IV, n = 60), and 32 women without endometriosis were served as control. Paired serum samples were also collected before the surgery. AMH in PF and serum were measured by ELISA. Individual clinical information was collected. AMH levels were compared according to the presence of endometriosis. The expression of AMHR2 in peritoneal endometriotic lesions obtained during laparoscopy was examined by immunohistochemistry. Results: AMH levels in PF were positively and significantly correlated with serum AMH levels in both women with and without endometriosis (R2 = 0.17, P < 0.0001; R2 = 0.30, P = 0.001, respectively). Serum AMH levels were inversely and significantly correlated with age in women with endometriosis (R2 = 0.092, P = 0.004) and in control women without statistical significance (R2 = 0.078, P = 0.12). AMH levels in PF were also inversely but not significantly correlated with age in women with and without endometriosis (R2 = 0.029, P = 0.11 and R2 = 0.027, P = 0.37, respectively). Mean age and serum AMH levels were not significantly different between two groups. On the other hand, AMH levels in PF were significantly lower in women with endometriosis compared to those of control women [2.15 ± 2.13 (mean ± SD) vs. 4.40 ± 4.77 ng/mL, P = 0.0001]. AMHR2 are localized at glandular epithelium and stromal cells in the ectopic endometrium of peritoneal endometriosis. Conclusions: Women with endometriosis may present lower PF AMH levels even if they retain serum levels similar to women without disease. As peritoneal endometriosis expresses a specific receptor for AMH, lower AMH levels in PF of women with advanced endometriosis may be involved in the pathophysiology of peritoneal endometriosis

Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified‐thawed human ovarian tissue xenografted to nude mice.

Purpose: Ovarian tissue cryopreservation and its auto-transplantation is promising technique in fertility preservation. Longevity of grafted tissue is limited though mechanism of follicle reduction is not fully understood. We evaluated histological alteration of vitrified-thawed ovarian tissue that grafted to nude mice. Materials and Methods: Human ovarian tissue was cryopreserved by vitrification. After thawing, they were grafted to mesentery of nude mice. Twelve weeks after transplantation, the implants were removed and histologically examined. The presence of follicles, the degree of fibrosis, and TUNEL staining in surrounding cortex were evaluated. The stromal expressions of alpha-smooth muscle actin (aSMA) were determined.Results: Normal ovarian cortex was decreased, and fibrotic area were significantly increased after grafting. The distributions of developmental stage of follicles shifted toward activation of follicular growth. Stromal TUNEL staining was increased in frozen/thawed tissue. The expression of aSMA were found in perifollicular stroma of growing follicles, which were decreased in grafted tissue associated with reduction of cortical stroma.Conclusions: Fibrosis, reduced cortical stroma, and activation of dormant follicleswere concomitantly observed in grafted ovarian cortex, which may relate to limited longevity. Perifollicular aSMA expression can be regarded as a marker of the competence of cortical stroma that regulate follicular development

A longitudinal, cross-sectional study of diversity in maternal platelet count kinetics, related to gestational thrombocytopenia

Background: Gestational thrombocytopenia (GT) is detected in approximately 8% of healthy pregnant women and >70% of pregnancy-associated thrombocytopenia cases. Diagnosed by exclusion, GT is primarily a benign disorder of unclear pathogenesis, although mechanisms have been proposed such as hemodilution. To better understand GT, we conducted retrospective longitudinal and cross-sectional analyses of variations in platelet count (PC) during gestation period. Methods: PC kinetics was assessed across a test group of 100 pregnant women, accurately representative of 341 in total, and in a control group of 200 non-pregnant women. Results: In the test group, median PC was comparable to the control group in early gestation but decreased by 8% by delivery day (DD). PC decreased by >5% in 59 pregnancies and increased by >5% in 19. 12 cases were thrombocytopenic. Median PC fluctuation, 2.5th percentile, and 97.5th percentile were each most extreme in final 5 weeks. Longitudinal analysis established five gestational pattern types defined by curvature and Change Ratio. The GT-type pattern (8 cases) showed relatively low PC in early gestation, mild downwards slope in the 2nd trimester, one or more peaks or “lifts” in the final weeks, followed by a “V-shape” of decrease beyond 15 x 104/μL to DD and sharp post-partum increase. Some of the GT-associated characteristics above appeared identifiable in a majority of pregnancies regardless of absolute PC value: Distinct PC “lift” occurring within the final ten weeks [later than in GT cases] followed by the V-shape [decrease to DD less pronounced than in GT], suggesting that diverse PC kinetics relate to the placental cytokine and receptor system. Conclusion: Our novel identification of diverse kinetic patterns in platelet count over gestational period suggests that, instead of a universal decrease caused by hemodilution alone, homeostatic conditions are affected by a diversity of varying factors such as the placental thrombopoietic system

Comprehensive immune complexome analysis detects disease-specific immune complex antigens in seminal plasma and follicular fluids derived from infertile men and women

Background: Autoimmune reactions and subsequent inflammation may underlie spermatogenic dysfunction and endometriosis-related infertility.The aim of this study is to identify disease-specific antigens in immune complexes (ICs) in seminal plasma (SP) and in follicular fluid (FF).Methods: Immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, was performed for specimens collected from infertile couples undergoing assisted reproduction.Forty-two male patients consisting of subjects with oligozoospermia (n=6), asthenozoospermia (n=8), and normal semen analysis (n=28). Fifty-eight female patients consisting of subjects with ovarian endometriosis (n=10) and control women without disease (n=48).Results: Four disease-specific antigens were identified in subjects with oligozoospermia, while five disease-specific antigens were detected in subjects with asthenozoospermia, some of which are involved in sprematogenesis. Eight antigens were detected only in subjects with endometriosis.Conclusion: Functional characteristics of disease-specific antigens were found to correspond to the pathogenesis of male and female infertility. The formation of ICs may contribute to spermatogenic dysfunction and endometriosis-related infertility via loss of function of the related proteins. Immune complexome analysis is expected to be a valuable tool for the investigation of novel diagnostic methods and treatment strategies for infertility

AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: a case report and review of literatures

Background: Androgen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated. Case presentation: Seventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence. Conclusions: Androgen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome