Association between Patients' Self-Judgement, Coagulated Menstrual Blood, and Menorrhagia: Results from a Questionnaire Survey and Blood Test Analysis.

Background and Objectives: Menorrhagia is defined as a blood loss of more than 80 mL, which is significant enough to cause anemia. Previously known methods for evaluating menorrhagia, such as the alkalin-hematin method, pictograms, and measuring the weight of sanitary products, were all impractical, complex, and time-consuming. Therefore, this study aimed to determine which item among menstrual history taking was most associated with menorrhagia and devised a simple evaluating method for menorrhagia through history taking that can be applied clinically. Materials and Methods: The study was conducted from June 2019 to December 2021. A survey was conducted on premenopausal women who underwent outpatient treatment or surgery and those who underwent a gynecologic screening test, and their blood tests were analyzed. The presence of iron deficiency anemia was identified with a Hb level of less than 10 g/dL with microcytic hypochromic anemia on a complete blood count performed within one month of the survey. A questionnaire survey was conducted on six items related to menorrhagia to investigate whether each item was related to "significant menorrhagia". Results: There were 301 participants in the survey during the period. In univariate analysis, the results revealed a statistically significant association between significant menorrhagia and the following items: self-judgement of menorrhagia; menstruation lasting over 7 days; total pad counts in a single menstrual period; Number of sanitary products changed per day; and leakaging of menstrual blood and presence of coagulated menstrual blood. In multivariate analysis, only the "self-judgement of menorrhagia" item showed a statistically significant result (p-value = 0.035; an odds ratio = 2.217). When the "self-judgement of menorrhagia" item was excluded, the "passage of clots larger than one inch in diameter" item showed a statistically significant result (p-value = 0.023; an odds ratio = 2.113). Conclusions: "Patient self-judgement of menorrhagia" is a reliable item for evaluating menorrhagia. Among several symptoms indicating menorrhagia, determining the presence of the "passage of clots larger than one inch in diameter" during the menstrual period is the most useful item for evaluating menorrhagia in clinical history taking. This study suggested using these simple menstrual history taking items to evaluate menorrhagia in real clinical practice.

Association between Preoperative 18-FDG PET-CT SUVmax and Next-Generation Sequencing Results in Postoperative Ovarian Malignant Tissue in Patients with Advanced Ovarian Cancer.

This study investigated the association between maximum standardized uptake values (SUVmax) on preoperative 18-FDG PET-CT and next-generation sequencing (NGS) results in post-surgical ovarian malignant tissue in patients with advanced ovarian cancer. Twenty-five patients with stage IIIC or IV ovarian cancer who underwent both preoperative 18-FDG PET-CT and postoperative NGS for ovarian malignancies were retrospectively enrolled. Two patients had no detected variants, 21 of the 23 patients with any somatic variant had at least one single nucleotide variant (SNV) or insertion/deletion (indel), 10 patients showed copy number variation (CNV), and two patients had a fusion variant. SUVmax differed according to the presence of SNVs/indels, with an SUVmax of 13.06 for patients with ≥ 1 SNV/indel and 6.28 for patients without (p = 0.003). Seventeen of 20 patients with Tier 2 variants had TP53 variants, and there was a statistically significant association between SUVmax and the presence of TP53 variants (13.21 vs. 9.35, p = 0.041). Analysis of the correlation between the sum of the Tier 1 and Tier 2 numbers and SUVmax showed a statistically significant correlation (p = 0.002; Pearson's r = 0.588). In conclusion, patients with advanced ovarian cancer with SNVs/indels on NGS, especially those with TP53 Tier 2 variants, showed a proportional association with tumor SUVmax on preoperative PET-CT.

Upregulation of SPI1 in Ectopic Endometrium Contributes to an Invasive Phenotype.

BACKGROUD AND AIM: Endometriosis is one of the most common gynecological diseases associated with chronic pelvic pain, infertility, and cancer. However, its molecular pathogenesis remains unclear. This study aimed to identify key genes involved in the pathogenesis of endometriosis. METHODS: Bioinformatic analyses were perfomed to identify key differentially expressed genes (DEGs), transcription factors (TFs), and functionally enriched pathways. Effect of SPI1 on migration, invasion, expression of ADH1B, MYH11, and PLN were analyzed in human endometriotic cells. RESULTS: By screening three transcriptome datasets from the GEO for overlapping DEGs between eutopic and ectopic endometria in patients with endometriosis, we found that the expression of ADH1B, MYH11, and PLN was markedly upregulated in the ectopic endometrium. Knockdown of ADH1B, MYH11, and PLN significantly inhibited the migration and invasion of human endometriotic 12Z cells. Additionally, gene set enrichment analysis revealed that epithelial-mesenchymal transition gene signature was positively correlated with ADH1B, MYH11, and PLN expression. Notably, the TF SPI1 was found to regulate the expression of these three genes in the endometriotic tissues and 12TZ cells. Moreover, SPI1 expression was associated with the invasion of endometriotic cells and was increased in the ectopic endometrium of patients with endometriosis. CONCLUSION: These data suggest that SPI1 plays a key role in the progression of endometriosis by regulating ADH1B, MYH11, and PLN expression and may therefore serve as a potential prognostic and therapeutic factor for endometriosis.

Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Preoperative Differential Diagnosis of Benign, Borderline, and Malignant Ovarian Tumors.

The purpose of this study was to investigate whether the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) can be used as supplementary tools to differentiate between benign, borderline, and malignant ovarian tumors. The ratio of patients with benign to borderline to malignant tumors was planned as 3:1:2 considering the incidence of each disease. Consecutive patients were enrolled retrospectively. Preoperative complete blood counts with differentials were investigated, and calculated NLRs and PLRs were analyzed. A total of 630 patients with ovarian tumors were enrolled in this study. The final histopathological results revealed that 318 patients had benign, 108 patients had epithelial borderline, and 204 patients had epithelial malignant ovarian tumors. The NLR and PLR were significantly higher in malignant than in benign or borderline ovarian tumors, and they did not differ significantly between benign and borderline ovarian tumors. The diagnostic cut-off value of NLR for differentiating between benign or borderline and malignant tumors was 2.36, whereas that of PLR for differentiating between benign/borderline and malignancy was 150.02. High preoperative NLR and PLR indicate that the likelihood of epithelial ovarian cancer is higher than that of benign or borderline tumors.

Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype.

High levels of iron in the peritoneal cavity during menstruation have been implicated in the pathogenesis of endometriosis. However, whether iron directly affects the growth or migration of human endometriotic cells is poorly understood. This study demonstrated the presence of increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with endometriosis. Furthermore, iron treatment stimulated the migration and epithelial-mesenchymal transition (EMT), but not growth, of 12Z human endometriotic cells. The expression of matrix metalloproteinase (MMP)-2/-9 was markedly increased through iron treatment in 12Z cells. Interestingly, intracellular reactive oxygen species (ROS) levels were significantly increased by iron in 12Z cells, and N-acetyl-L-cysteine significantly reduced iron-induced migration and MMP-2/-9 expression. Additionally, iron stimulated the activation of the NFκB pathway, and the activation was associated with iron-induced migration and MMP-2/-9 expression in 12Z cells. Moreover, iron markedly increased EMT and MMP-2/-9 expression in endometriotic lesions in an endometriosis mouse model. Taken together, these results suggest that iron may contribute to the migration abilities of human endometriotic cells via MMP expression through the ROS-NFκB pathway.

Prognosis-Predicting Model Based on [18F]fluorodeoxyglucose PET Metabolic Parameters in Locally Advanced Cervical Cancer Patients Treated with Concurrent Chemoradiotherapy: Multi-Center Retrospective Study.

This study aimed to develop a prognosis-predicting model based on [18F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and clinicopathologic factors in locally advanced cervical cancer patients treated with concurrent chemoradiotherapy (CCRT). The medical records of 270 locally advanced cervical cancer patients who were treated with CCRT were collected from three institutions and reviewed retrospectively. A nomogram was used for predicting 2-year disease-free survival (DFS) and 5-year overall survival (OS) based on Cox proportional hazards regression. Predictor variables included nodal maximum standardized uptake value (SUVmax), primary tumor SUVmax, age, tumor size, stage, serum squamous cell carcinoma antigen level, and human papillomavirus status. Internal nomogram validation was performed. A nomogram for predicting the 2-year DFS and 5-year OS was constructed using six and seven parameters, respectively. With a focus on 2-year DFS, our model found nodal SUVmax to be the highest weighted negative prognostic factor. With a focus on 5-year OS, young age was the highest weighted negative prognostic factor. The concordance index was 0.75 and 0.78 for the 2-year DFS and 5-year OS, respectively. This nomogram is a predictive tool that can be used to counsel patients for predicting survival outcomes. Moreover, our prognosis-predicting model may make it possible to personalize treatment.

Clinical significance of lymph node size in locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Background: This study aimed to assess the in-field lymph node (LN) failure rate according to LN size and to investigate effect of LN size on the survival outcome of patients with locally advanced cervical carcinoma treated with concurrent chemoradiotherapy (CCRT). Methods: A total of 310 patients with locally advanced cervical carcinoma treated with CCRT were enrolled in retrospective study. LN status was evaluated by magnetic resonance imaging. All patients received conventional external beam irradiation and high-dose rate brachytherapy, and concurrent cisplatin-based chemotherapy. In-field LN failure rate according to LN size was analyzed. Results: The median follow-up period was 83 months (range, 3-201 months). In-field LN failure rate in patients with pelvic LN size more than 10 mm was significantly higher than that in patients with pelvic LN size less than 10 mm (p<0.001). A similar finding was observed in the in-field para-aortic LN (PALN) failure rate (p=0.024). The pelvic and PALN size (≥10 mm) was a significant prognostic factor of overall-survival (OS) and disease-free survival rate in univariate and multivariate analyses. The OS rate was significantly different between groups according to LN size (<10 mm vs. ≥10 mm). Conclusion: A LN of less than 10 mm in size in an imaging study is controlled by CCRT. On the other hand, in LN of more than 10 mm in size, the in-field LN failure rate increase and the prognosis deteriorate. Therefore, a more aggressive treatment strategy is needed.

Hepatocyte nuclear factor-1 beta protects endometriotic cells against apoptotic cell death by up-regulating the expression of antiapoptotic genes†.

The overexpression of hepatocyte nuclear factor-1 beta (HNF1ß) in endometriotic lesion has been demonstrated. However, the role of HNF1ß in endometriosis remains largely unknown. Human endometriotic 12Z cells showed higher level of HNF1ß when compared with normal endometrial HES cells. In human endometriotic 12Z cells, HNF1ß knockdown increased susceptibility to apoptotic cell death by oxidative stress, while HNF1ß overexpression suppressed apoptosis. In addition, HNF1ß knockdown and overexpression significantly decreased and increased, respectively, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent antiapoptotic genes. Knockdown of the antiapoptotic genes significantly reduced the HNF1ß-induced resistance against oxidative stress in 12Z cells. Furthermore, HNF1ß regulated the transcriptional activity of NF-κB, and an NF-κB inhibitor suppressed the HNF1ß-enhanced NF-κB-dependent antiapoptotic gene expression and the resistance of the 12Z cells against cell death. Taken together, these data suggest that HNF1ß overexpression may protect endometriotic cells against oxidative damage by augmenting antiapoptotic gene expression.

Iloprost, a prostacyclin analog, inhibits the invasion of ovarian cancer cells by downregulating matrix metallopeptidase-2 (MMP-2) through the IP-dependent pathway.

Recent studies have shown that a bioactive lipid prostacyclin (PGI2) plays a role in various cancers, including lung cancer. However, the specific function of PGI2 in ovarian cancer progression has not been determined. This study investigated the effects of PGI2 on cell growth, migration, and invasion in ovarian cancer cells using iloprost, a stable PGI2 analog. Iloprost significantly inhibited migration and invasion, but not cell growth, in a dose-dependent manner in human ovarian cancer cells (A2780 and SKOV3). Interestingly, the cell surface Gs protein-coupled PGI2 receptor IP was enhanced in human ovarian cancer cells. The inhibitory effect of iloprost on migration and invasion was entirely reversed by an IP antagonist (CAY10449) and IP siRNA, whereas the knockdown of peroxisome proliferator-activated receptor δ (PPARδ), a nuclear receptor of PGI2, did not rescue the effect of iloprost. Additionally, iloprost markedly decreased the expression of matrix metallopeptidase-2 and -9 (MMP-2 and MMP-9), which may be induced in the process of ovarian cancer metastasis. IP siRNA inhibited iloprost-reduced MMP-2 expression but not MMP-9 expression. Moreover, inhibition of protein kinase A (PKA) and overexpression of Akt and p38 rescued the inhibition of invasion and the reduction of MMP-2 expression by iloprost. Furthermore, iloprost-induced activation of PKA was associated with PKA-mediated Akt and p38 inactivation in ovarian cancer cells. Taken together, these results demonstrate that iloprost inhibits ovarian cancer cell invasion by downregulating MMP-2 expression via the IP-mediated PKA pathway. This study is the first to reveal a novel role for iloprost and to clarify its underlying mechanism in human ovarian cancer cells.

Prophylactic extended-field irradiation with concurrent chemotherapy for pelvic lymph node-positive cervical cancer.

PURPOSE: This study aimed to evaluate whether prophylactic extended-field pelvic radiotherapy (EF-PRT) yields better results than standard whole pelvic radiotherapy (WPRT) in patients with pelvic lymph node-positive cervical cancer treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 126 cases of stage IB-IVA cervical cancer that had pelvic lymph node involvement in magnetic resonance imaging and were treated with CCRT between 2000 and 2016 were reviewed. None of the patients had paraaortic lymph node (PALN) metastases. The patients were classified to two groups, namely, those treated with EF-PRT, including prophylactic para-aortic radiotherapy, and those treated only with WPRT. The median dose to the PALN area in patients treated with EF-PRT was 45 Gy. All patients received concurrent cisplatin-based chemotherapy. RESULTS: Overall, 52 and 74 patients underwent EF-PRT and WPRT, respectively. Patient characteristics and irradiated dose were not significantly different, except the dose to the para-aortic area, between the two groups. The median follow-up period was 75.5 months (range, 5 to 195 months). The 10-year cumulative recurrence rate of PALN for EF-PRT vs. WPRT was 6.9% and 10.1% (p = 0.421), respectively. The 10-year disease-free survival and overall survival for EF-PRT vs. WPRT were 69.7% vs. 66.1% (p = 0.748) and 71.7% vs. 72.3% (p = 0.845), respectively. Acute gastrointestinal complications were significantly higher in EF-PRT (n = 21; 40.4%) than WPRT (n = 26; 35.1%) (p = 0.046). Late toxicities were not significantly different in both groups. CONCLUSION: In this study, prophylactic radiotherapy for PALN does not have an additional benefit in patients with pelvic lymph node-positive cervical cancer treated with CCRT.

Interleukin 6 secretion from alternatively activated macrophages promotes the migration of endometriotic epithelial cells.

Accumulating evidence has suggested an interaction between endometriotic cells and macrophages in the endometriotic microenvironment and the potential role of this interaction in the pathogenesis of endometriosis. However, how endometriotic cells communicate with macrophages to influence their function is poorly understood. In the present study, we found that the mRNA expression and production of CC chemokine ligand 2 (CCL2) were much higher in human endometriotic epithelial cells (11Z and 12Z) than those in human endometrial epithelial cells (HES). The inhibition of CCL2 action using neutralizing antibodies substantially suppressed macrophage migration induced by endometriotic epithelial cells. The endometriosis-associated macrophages (EAMs), which are the macrophages that are stimulated by the conditioned medium (CM) of human endometriotic cells, highly expressed the M2 phenotype markers (MRC1 and TREM2). In addition, the CM of EAMs significantly increased cell migration in 12Z cells, but no significant change was observed in cell growth. RT-PCR and antibody array analyses revealed that EAMs highly express and produce interleukin (IL) 6 compared to macrophages stimulated by the CM of HES cells. Moreover, the EAM-CM-induced migration and MMP2/9 expression in endometriotic cells were significantly attenuated by IL6 signaling inhibition. These results suggest a reciprocal activation of macrophages and endometriotic cells via the soluble factors CCL2 and IL6, which may contribute to the development of endometriosis.

Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation.

OBJECTIVE: The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. METHODS: A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. RESULTS: Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). CONCLUSION: Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival.

Intrapelvic dissemination of early low-grade endometrioid stromal sarcoma due to electronic morcellation.

Endometrioid stromal sarcoma is a rare malignancy that originates from mesenchymal cells. It is classified into low-grade endometrioid stromal sarcoma (LGESS) and high-grade endometrioid stromal sarcoma. Ultrasonographic findings of LGESS resemble those of submucosal myomas, leading to the possible preoperative misdiagnosis of LGESS as uterine leiomyoma. Electronic morcellation during laparoscopic surgery in women with LGESS can result in iatrogenic intraabdominal dissemination and a poorer prognosis. Here, we report a patient with LGESS who underwent a supracervical hysterectomy and electronic morcellation for a presumed myoma in another hospital. Disseminated metastatic lesions of LGESS in the posterior cul-de-sac and rectal serosal surface were absent on primary surgery, but found during reexploration. In conclusion, when LGESS is found incidentally following previous morcellation during laparoscopic surgery for presumed benign uterine disease, we highly recommend surgical reexploration, even when there is no evidence of a metastatic lesion in imaging studies.

Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway.

Despite evidence that leptin may play a role in the pathogenesis of endometriosis, the specific function of leptin in the migration and invasion of endometriotic cells is not well characterized. In this study, we investigated the effect of leptin on the migration, invasion and matrix metalloproteinase (MMP) expression levels of human endometriotic cells. We found that leptin stimulated the migration and invasion of endometriotic cells (11Z, 12Z and 22B) in a dose-dependent manner. Leptin receptor (ObR) siRNA significantly inhibited the migration and invasion induced by leptin in 11Z and 12Z cells. Leptin-induced migration and invasion were significantly attenuated by pretreatment with SB-3CT, a specific gelatinase (MMP-2 and MMP-9) inhibitor. In addition, leptin-induced increases in the mRNA and protein expression and enzyme activity of MMP-2 in 11Z and 12Z cells. Selectively inhibiting MMP-2 using siRNA and an inhibitor (GM6003), impaired the ability of leptin to stimulate the migration and invasion of endometriotic cells, suggesting that MMP-2 plays an essential role in leptin-induced migration and invasion. Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) inhibitor (AG490) significantly inhibited the migration, invasion and MMP-2 expression induced by leptin in endometriotic cells. Furthermore, the Extracellular signal-Regulated Kinase inhibitor PD98059 neutralized the migration and invasion promoting effects of leptin. Taken together, these results suggest that leptin may contribute to the migration and invasion abilities of endometriotic cells via the up-regulation of MMP-2 through an ObR-dependent JAK2/STAT3 signaling pathway.

Brown algae phlorotannins enhance the tumoricidal effect of cisplatin and ameliorate cisplatin nephrotoxicity.

OBJECTIVE: The clinical application of cisplatin is limited due to its drug resistance and side effects. We investigated the effect of a phlorotannin-rich extract from the edible brown alga Ecklonia cava (PREC) and its major phlorotannin (dieckol) on cisplatin responsiveness and side effects. METHODS: The A2780 and SKOV3 ovarian cancer cell lines and the SKOV3-bearing mouse model were used. The MTT assay was applied to assess cell viability, and the annexin V assay was employed for apoptosis analysis. Reactive oxygen species (ROS) production and protein expression were assessed by H2DCFDA staining and Western blotting, respectively. RESULTS: We found that PREC enhanced the tumor growth-inhibitory effect of cisplatin and diminished cisplatin-induced nephrotoxicity and weight loss in SKOV3-bearing mice. PREC augmented cisplatin-induced apoptosis by activating caspases in SKOV3 and A2780 ovarian cancer cells. In addition, a combination of PREC and cisplatin-induced ovarian cancer cell apoptosis by downregulating the Akt and NFκB pathways. We further demonstrated that PREC increased intracellular ROS and that antioxidants significantly attenuated Akt-NFκB activation and apoptosis in ovarian cancer cells. In contrast, PREC inhibited cisplatin-induced ROS production and cell death in normal HEK293 kidney cells. Dieckol, a major compound in PREC, significantly enhanced the inhibition of tumor growth by cisplatin with less weight loss and kidney damage in a mouse model. CONCLUSION: These data suggest that brown algae phlorotannins may improve the efficacy of platinum drugs for ovarian cancer by enhancing cancer cell apoptosis via the ROS/Akt/NFκB pathway and reduce nephrotoxicity by protecting against normal kidney cell damage.

High expression of epidermal growth factor-like domain 7 is correlated with poor differentiation and poor prognosis in patients with epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to evaluate the expression of epidermal growth factor-like domain 7 (EGFL7) in epithelial ovarian cancer, and to assess its relevance to clinicopathological characteristics and patients' survival. METHODS: A total of 177 patients with epithelial ovarian cancer were enrolled in the current study. For each patient, a retrospective review of medical records was conducted. Immunohistochemical staining for EGFL7 was performed using tissue microarrays made with paraffin-embedded tissue block. EGFL7 expression levels were graded on a grade of 0 to 3 based on the percentage of positive cancer cells. We analyzed the correlations between the expression of EGFL7 and various clinical parameters, and also analyzed the survival outcome according to the EGFL7 expression. RESULTS: The expression of EGFL7 in ovarian cancer tissues was observed in 98 patients (55.4%). High expression of EGFL7 (grade 2 or 3) was significantly correlated with pathologic type, differentiation, stage, residual tumor after debulking surgery, lymphovascular space involvement, lymph node metastasis, high cancer antigen 125, peritoneal cytology, and ascites. Among these clinicopathologic factors, differentiation was significantly correlated with EGFL7 expression in multivariate analysis (p<0.05). Survival analysis showed that the patients with high EGFL7 expression had a poorer disease free survival than those with low EGFL7 expression (p=0.002). CONCLUSION: Our data suggest that EGFL7 expression is a novel predictive factor for the clinical progression of epithelial ovarian cancer, and may constitute a therapeutic target for antiangiogenesis therapy in patients with epithelial ovarian cancer.

Ovarian angioleiomyoma: a case report.

Angioleiomyoma (ALM) is a rare and painful, benign neoplasm that is referred to an uncommon type of leiomyoma originating from smooth muscle cells of arterial and venous walls. ALM is very rarely found in the female genital organs such as uterus or ovary. Herein, we present the case of a huge primary ovarian ALM in a 35 year-old woman, clinically and radiologically mimicking an ovarian fibroma, which histologically has diffuse myxoid degeneration. This is the third case of ovarian ALM and the first case of ovarian ALM with diffuse degeneration reported in English literatures, to the best of our knowledge.

Expression of adiponectin, leptin, and their receptors in ovarian endometrioma.

OBJECTIVE: To evaluate the expression of leptin, leptin receptor (ObR), adiponectin, and adiponectin receptor (AdipoR) in ovarian endometriomas compared with normal endometrium, and to analyze relationships among adipokines and their receptors. DESIGN: Experimental study. SETTING: A clinic for the treatment of endometriosis and basic research laboratories. PATIENT(S): Forty-four women with endometriosis and 42 age-matched women with no laparoscopic evidence of endometriosis as control subjects. INTERVENTION(S): Endometrial tissue samples were obtained during laparoscopic surgery. MAIN OUTCOME MEASURE(S): Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed with the use of tissue microarray. Clinical characteristics were reviewed from the patient's medical records. The effect of leptin on the expression of adiponectin was evaluated in endometriotic cell line using real-time reverse-transcription polymerase chain reaction. RESULT(S): Positive expression rates of leptin and ObR were significantly higher in ovarian endometrioma compared with normal endometrium, but those of adiponectin and AdipoR were similar (ovarian endometrioma vs. normal endometrium, respectively: leptin 100% vs. 59.5%; ObR 72.7% vs. 33.3%; adiponectin 31.8% vs. 42.9%; AdipoR 88.6% vs. 73.8%). Expression of adipokines and their receptors did not show any correlation with disease stage. A positive correlation was found between expression of ObR and adiponectin (correlation coefficient 0.488; P=.001). Leptin treatment in endometriotic cells induced mRNA expression of adiponectin. CONCLUSION(S): These data suggest that leptin and its receptor are induced in ovarian endometriomas, and that the leptin/ObR system regulates adiponectin gene expression in endometriotic cells.

Resonant amplification of vortex-core oscillations by coherent magnetic-field pulses.

Vortex structures in soft magnetic nanodisks are highly attractive due to their scientific beauty and potential technological applications. Here, we experimentally demonstrated the resonant amplification of vortex oscillations by application of simple coherent field pulses tuned to optimal width and time intervals. In order to investigate vortex excitations on the sub-ns time scale, we employed state-of-the-art time-resolved full-field soft X-ray microscopy of 70 ps temporal and 25 nm lateral resolution. We found that, due to the resonant enhancement of the vortex gyration motion, the signal input power can be significantly reduced to ~ 1 Oe in field strength, while increasing signal gains, by increasing the number of the optimal field pulses. We identified the origin of this behavior as the forced resonant amplification of vortex gyration. This work represents an important milestone towards the potential implementation of vortex oscillations in future magnetic vortex devices.

Leptin receptor is induced in endometriosis and leptin stimulates the growth of endometriotic epithelial cells through the JAK2/STAT3 and ERK pathways.

Leptin acts as a potential growth stimulator in several normal and neoplastic cells. Recent studies have shown the presence of increased levels of leptin in the peritoneal fluid of patients with endometriosis, implicating leptin in the pathogenesis of endometriosis. However, the specific function of leptin in the induction of mitogenesis in endometriosis is not known. This study investigated the expression of the leptin receptor (ObR) in endometrioma tissues and immortalized endometriotic cells, and the effect of leptin on cell growth. ObR expression was higher in endometriomas than in the normal endometrium, and it was detected in 74% of epithelial and 30% of stromal endometrioma tissues. In addition, human endometriotic epithelial cells (11Z and 12Z) showed a high level of ObR when compared with endometrial cells and endometriotic stromal cells (22B). Furthermore, leptin treatment stimulated the growth of 11Z and 12Z cells, but not that of 22B cells. Knockdown of the ObR in 11Z and 12Z cells impaired the ability of leptin to induce cell growth. Leptin induced the activation of Janus Kinases 2 (JAK2), signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) in endometriotic epithelial cells. Moreover, pretreatment with the JAK2/STAT3 inhibitor AG490 and the ERK inhibitor PD98059 significantly inhibited leptin-induced cell growth. The present results show that the ObR is induced in endometriosis, and that leptin stimulates the growth of endometriotic epithelial cells through the JAK2/STAT3 and ERK pathways.