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Abstract Background Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established. Studies have explored the potential use of serological metabolites as biomarkers of MASH severity in relation to human MASH. Methods We performed a comparative analysis of three mouse models of diet-induced MASH in terms of phenotypic and metabolomic characteristics; MASH was induced using different diets: a high-fat diet; a Western diet; and a high-fat, high-cholesterol diet. Liver cirrhosis was diagnosed using standard clinical approaches (e.g., METAVIR score, hyaluronan level, and collagen deposition level). Mouse serum samples were subjected to nuclear magnetic resonance spectroscopy–based metabolomic profiling followed by bioinformatic analyses. Metabolomic analysis of a retrospective cohort of patients with hepatocellular carcinoma was performed; the corresponding cirrhosis scores were also evaluated. Results Using clinically relevant quantitative diagnostic methods, the severity of MASH was evaluated. Regarding metabolomics, the number of lipoprotein metabolites increased with both diet and MASH progression. Notably, the levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) significantly increased with fibrosis progression. During the development of diet-induced MASH in mice, the strongest upregulation of expression was noted for VLDL receptor. Metabolomic analysis of a retrospective cohort of patients with cirrhosis indicated lipoproteins (e.g., VLDL and LDL) as predominant biomarkers of cirrhosis. Conclusions Our findings provide insight into the pathophysiology and metabolomics of experimental MASH and its relevance to human MASH. The observed upregulation of lipoprotein expression reveals a feedforward mechanism for MASH development that may be targeted for the development of noninvasive diagnosis.

Objective: Ovarian clear cell carcinoma has a poor prognosis in comparison with other pathological types of epithelial ovarian carcinoma. It also has relative resistance to first-line platinum-based chemotherapy with a great risk of recurrence. Case report: We report a case of recurrent ovarian clear cell carcinoma status after left salpingo-oophorectomy (fertility-sparing debulking operation) and six courses of adjuvant chemotherapy (paclitaxel (175 mg/m2)/carboplatin (AUC 6)). However, two years after diagnosis, elevated CA-125 accompanied by an intrapelvic mass was noted. Uterine intramural recurrence was found during the second laparotomy. She was treated with right salpingo-oophorectomy and abdominal hysterectomy combined with systemic chemotherapy administration (paclitaxel (175 mg/m2)/carboplatin (AUC 6)) and maintenance therapy (bevacizumab (7.5 mg/kg)). There was no other recurrence until one and a half years postoperatively, and the patient was tumor free with regular follow-up. Conclusion: In young patients with stage I ovarian clear cell carcinoma, fertility-sparing surgery was considered. Most patients will suffer from tumor recurrence, and also intrauterine recurrence rarely happen.

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates showed that the compound was well distributed in a spontaneous HCC mouse model. Therefore, a rationale design was developed for chemically synthesizing a linoleate-pazopanib conjugate (LAPC). The LAPC showed a significantly improved cytotoxicity compared to the parental drug pazopanib. Pazopanib’s angiogenic suppressing signals were not observed in LAPC-treated HCC cells, potentially suggesting an altered mechanism of action (MOA). In an efficacy trial comparing placebo, oral pazopanib, and LAPC treatments in the hepatitis B virus transgene-related spontaneous HCC mouse model (HBVtg-HCC), the LAPC treatment demonstrated superior tumor ablating capacity in comparison to both placebo and pazopanib treatments, without any discernible systemic toxicity. The LAPC exposure is associated with an apoptosis marker (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) and an enhanced ferroptosis (glutathione peroxidase 4 [GPX4]) potential in HBVtg-HCC tumors. Therefore, the LAPC showed excellent HCC ablative efficacy with altered MOA. The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.

Objective: To evaluate efficacy of stereotactic body radiotherapy (SBRT) for pelvic boost irradiation in gynecological cancer patients with pelvic recurrence or with intact uterus unsuitable for brachytherapy. Materials and methods: We retrospectively reviewed the medical records of 25 gynecological cancer patients who received SBRT boost for pelvic recurrence (salvage group, n = 14), or for local dose escalation instead of intracavitary brachytherapy due to unfavorable medical condition (definitive group, n = 11). The pelvis was irradiated with a median dose of 54 Gy in six weeks, and then SBRT was prescribed with a range of 10–25Gy in two to five fractions. The cumulative radiobiological equivalent dose in 2-Gy fractions (EQD2) to the tumors ranged from 62.5 to 89.5 Gy10 (median, 80.7). Overall survival (OS) and in-field relapse-free survival (IFRFS) were calculated using the Kaplan–Meier method. Results: At the initial assessment, eighteen (72%) patients achieved complete or partial remission, and seven (28%) had stable or progressive disease. With a median follow duration of 12 months, the 1-year IFRFS for salvage and definitive group were 64.5% and 90.0%, whereas the 1-year OS for the two groups were 80.8% and 49.1%, respectively. One patient developed entero-vaginal fistula and one had sigmoid perforation. No patient experienced ≧ grade 3 genitourinary complications. Conclusion: In gynecological cancer patients with recurrent pelvic tumors or intact uterus unsuitable for brachytherapy, local dose escalation with SBRT resulted in an initial response rate of 72% with acceptable early toxicities. A long-term follow-up is required to assess the impact on local control or survival.

Abstract Cholesterol affects cancer progression, and acetyl‐CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl‐CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan–Meier Plotter web‐based gene survival analyzer and The Cancer Genome Atlas (TCGA)‐database analyzed with DBdriver.v2 platform, we revealed acetyl‐CoA production and the mevalonate pathway are associated with GCa prognosis. We found mitochondrial‐derived acetyl‐CoA contributing enzymes (acyl‐coA synthetase super‐family 3; ACSS3) is the GCa progression confounder. Interestingly, it is not HMGCR (the committee enzyme of mevalonate pathway), but lower mevalonate pathway enzymes (e.g., MVK, LSS, DHCR14A1, SC4MOL, HSD17B7, SC5D) promote GCa patients 5‐years overall survival in a differential level. Advanced analyses found ACSS3 is prognosis biosignatures for multiple GCa disease conditions. This report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions, which implicates a targeting value for GCa therapy. While knockdown ACSS3 could suppress growth and invasion of GCa cells, of which even more impactful under starvation condition. This is the first report, surprisingly, revealed ACSS3 as important cancer prognosis biomarker. Targeting ACSS3 could be a novel therapeutic strategy for cancer, in this case, GCa.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA.

Abstract Background Breast and cervical cancer are the most common cancers affecting women. The symptom distresses experienced by cancer survivors are critical factors influencing their quality of life (QOL). This study investigated the QOL of breast and cervical cancer survivors, their physical, psychological and social conditions. Methods The participants were older than 20 years, had been diagnosed with breast or cervical cancer for more than 2 years, and had completed their cancer treatment. The survey incorporated the QOL questionnaires developed by the European Organization of Research and Treatment for Cancer and a self-designed questionnaire. Results The mean age at diagnosis was 48.89 ± 8.53 years for the breast cancer survivors and 49.00 ± 10.30 years for the cervical cancer survivors. The corresponding QOL scores were 75.33 ± 20.25 and 75.56 ± 17.93. The factors influencing QOL of breast cancer survivors were household income, number of comorbidities, stage of cancer, type of cancer treatment and duration of illness, whereas the factor related to QOL of cervical cancer survivors was only household income. Conclusions The QOL of the two groups was similar. Healthcare providers should demonstrate greater concern toward breast and cervical cancer survivors.

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

Endometrial stromal tumors are rare uterine tumors (

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.

Objective: The aim of this study is to evaluate the long-term outcome of ovarian recurrent granulosa cell tumors (GCTs) in a large series of patients treated in Taiwanese Gynecologic Oncology Group (TGOG) centers and to define the prognostic parameters for survival. Materials and methods: A retrospective multi-institutional review of patients with recurrent ovarian GCTs treated in TGOG centers was conducted. The clinical and pathological characteristics, treatment, and outcomes of patients with ovarian recurrent GCTs were analyzed using Kaplan-Meier and Cox proportional hazards analyses to determine the predictors for survival. Results: A total of 44 patients from 16 medical centers were identified between January 1994 and December 2010. The median disease-free survival (DFS), postrecurrence survival, and overall survival (OS) were 61.5 months (range, 3.7–219.3 months), 55.8 months (range, 4.6–193.7 months), and 115.3 months (range, 17.2–390.6 months), respectively. In multivariate analysis, DFS (> 61.5 months versus ≤ 61.5 months, hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.03–0.78, p = 0.024) at the initial operation after diagnosis of relapse was the only predictor that correlated with OS. Conclusion: DFS after the initial operation was the only important predictor for overall survival in patients with recurrent GCTs, regardless of treatment, suggesting that the natural behavior of the tumor is a critical factor for patients with recurrent GCTs.

Objective: Use of vaginal meshes for treatment of pelvic organ prolapse (POP) remains controversial. A trend toward abdominal approaches and the development of new meshes has been noted. We compared the 1-year results of two different approaches using new lightweight meshes. Materials and methods: Sixty-nine (95.8%) of 72 women with POP Stage ≥ 2, who underwent laparoscopic sacrocolpopexy (LSC) (n = 39) or a total vaginal mesh (TVM) procedure (n = 30) using lightweight polypropylene meshes, were studied. Baseline and follow-up assessments included a pelvic examination and a composite condition-specific questionnaire. A detailed comparison of 1-year outcomes was made. Data were analyzed using appropriate statistical methods. Results: Compared to the TVM group, the LSC group was characterized by a younger age (53.7 years vs. 64.1 years, p

Background: Ovarian teratocarcinoma (OVTC) arises from germ cells and contains a high percentage of cancer stem/progenitor cells (CSPCs), which promote cancer development through their ability to self-renew. Androgen and androgen receptor (androgen/AR) signaling has been reported to participate in cancer stemness in some types of cancer; however, this phenomenon has never been studied in OVTC. Methods: Ovarian teratocarcinoma cell line PA1 was manipulated to overexpress or knockdown AR by lentiviral deliver system. After analyzing of AR expression in PA1 cells, cell growth assay was assessed at every given time point. In order to determine ligand effect on AR actions, luciferase assay was performed to evaluate endogenous and exogenous AR function in PA1 cells. CD133 stem cell marker antibody was used to identify CSPCs in PA1 cells, and AR expression level in enriched CSPCs was determined. To assess AR effects on CD133+ population progression, stem cell functional assays (side population, sphere formation assay, CD133 expression) were used to analyze role of AR in PA1 CSPCs. In tissue specimen, immunohistochemistry staining was used to carry out AR and CD133 staining in normal and tumor tissue. Results: We examined androgen/AR signaling in OVTC PA1 cells, a CSPCs-rich cell line, and found that AR, but not androgen, promoted cell growth. We also examined the effects of AR on CSPCs characteristics and found that AR expression was more abundant in CD133+ cells, a well-defined ovarian cancer stem/progenitor marker, than in CD133− populations. Moreover, results of the sphere formation assay revealed that AR expression was required to maintain CSPCs populations. Interestingly, this AR-governed self-renewal capacity of CSPCs was only observed in CD133+ cells. In addition, we found that AR-mediated CSPCs enrichment was accompanied by down-regulation of p53 and p16. Finally, co-expression of AR and CD133 was more abundant in OVTC lesions than in normal ovarian tissue. Conclusion: The results of this study suggest that AR itself might play a ligand-independent role in the development of OVTC.

Objective: To report the natural history and prognosis of the uncommon Sertoli–Leydig cell tumor (SLCT) of the ovary. Materials and Methods: A 20-year retrospective review was conducted by the Taiwanese Gynecologic Oncology Group (TGOG), including nine tertiary medical centers from different regions in Taiwan. The medical records for 40 cases of ovarian SLCT were collected. Pathology reviews were carried out by a panel of expert pathologists. Results: After pathological review, 17 patients were subsequently excluded because the pathology slides were unavailable in five cases, and discrepant results from the initial diagnosis were found in 12 cases (34%). For the remaining 23 patients, the median age was 41 years. The most common symptom was irregular vaginal bleeding followed by an abdominal mass or amenorrhea. Most of the tumors were unilateral and confined to the right ovary, with an average size of 8.2 cm. Preoperative serum markers were available for 12 patients and were elevated for three patients. All patients underwent primary surgery. Six patients accepted adjuvant chemotherapy, and bleomycin, etoposide, and cisplatin were used in four of them. Clinical follow-up information was available in 21 patients with a median of 19 months. Eighty-two percent of patients were alive and free of disease up to the date of the last follow-up. Two patients died of the disease. Conclusion: This study demonstrates the extreme rarity of ovarian SLCT in Taiwan. Histological discordance between the diagnosis and central review proves the need for expertise review before treatment. For an improved understanding of the biological behavior and treatment strategy for this unique tumor, international collaboration is imperative.

Objective: To assess risk factors for postoperative pelvic cellulitis in women undergoing laparoscopic-assisted vaginal hysterectomy (LAVH). Materials and Methods: A total of 195 patients who underwent LAVH for benign gynecological diseases during the period 2007–2008 were enrolled. Among them, 11 patients developed pelvic cellulitis (group 1, cases) and 184 did not (group 2, controls). Results: The proportion of patients in American Society of Anesthesiologists physical status scale (ASA) class II was significantly higher in group 1 (p=0.017). The grade of pelvic adhesion was significantly more severe in group 1 (p=0.044). The mean length of hospital stay in group 1 was significantly longer than in group 2. Logistic regression analysis revealed that patients in ASA class II were six times more likely to develop postoperative pelvic cellulitis than patients in ASA class I. In addition, the analysis showed that there was a twofold increase in risk for pelvic cellulitis with each single-grade increase in the degree of pelvic adhesion. Women with postoperative pelvic cellulitis also had a significantly increased length of hospital stay. Conclusion: Understanding the risk factors for postoperative pelvic infection, such as systemic disease, pelvic adhesion, and prolonged hospital stay, comprehensive care of patients, and correction of modifiable risk factors will help reduce the rate of postoperative pelvic cellulitis in women undergoing LAVH.

Objective: The anti-proliferation effect of caffeic acid (3,4-dihydroxycinnamic acid), isolated from Ocimum gratissimum Linn, on human cervical cancer cells (HeLa cells) was examined to elucidate the associated mechanism and death mode. Materials and Methods: Flow cytometry showed that caffeic acid treatment results in dramatically increased apoptosis of HeLa cells. Western blot analysis revealed that caffeic acid activates various processed caspases. Results: Caffeic acid significantly reduced proliferation of HeLa cells in a concentration-dependent manner. Morphological evidence of apoptosis, including nuclei fragmentation was clearly observed 24 and 48 hours after exposure to caffeic acid (1 mM and 10 mM) by flow cytometry. Time-dependent inhibition was also observed. Caffeic acid decreased levels of uncleaved caspase-3 and Bcl-2, and induced cleaved caspase-3 and p53. Conclusion: Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

Objective: Ocimum gratissimum is a herbal medicine and caffeic acid (3,4-dihydroxycinnamic acid) is one of its main components. Caffeic acid is known to control the levels of cholesterol and triglycerides, reduce the activity of cancer cells, and enhance immunity in the human body. The amounts of caffeic acid in herbal medicine and vegetable oils have not been reported in the literature since an analytical method has not yet been established. In this study, we explored the effects of caffeic acid treatment on anti-proliferation in HeLa cells. Materials and Methods: This paper presents a method of extraction of caffeic acid from O. gratissimum and Ju ZenTa (Ocimum basilicum L.) using high performance liquid chromatography. Treatment of HeLa cells with the extracted caffeic acid (10 mM) was analyzed. Results: We showed that caffeic acid isolated from several kinds of vegetables and from the herb of O. gratissimum had anti-proliferative effects on cervical cancer cell lines. Caffeic acid can significantly reduce the proliferation of HeLa cells in a time-dependent manner. Conclusion: This paper shows that high performance liquid chromatography is a suitable analytical method for determining caffeic acid levels in O. gratissimum, Ju ZenTa, and several vegetable oils. Caffeic acid can suppress the proliferation of HeLa cells.

Background: Human ovarian carcinoma is a silent killer. Most patients with human ovarian carcinoma are diagnosed in the advanced stages. Currently, no effective means of early detection are available. Identifying genes that distinguish early cancers from normal tissue may provide insight to the initiation and progression of ovarian cancer. Methods: A large-scale gene expression profiling using 9,600 genes-complementary DNA array to study ovarian tumors was conducted. We analyzed 13 benign tumors, 22 invasive cancers (seven stage I and 15 stage III), and 16 normal ovaries. Cluster analysis revealed two major groups: the early-stage cluster that included 13 benign tumors and seven stage I cancers; and the late-stage cluster that included all stage III cancers. Results: There were 433 upregulated and 60 downregulated genes from the early-stage cluster, and 395 upregulated and 101 downregulated genes from the late-stage cluster. These genes showed altered functions for tumor/cancers, functions such as cell growth, cell cycle control, differentiation, signaling, apoptosis, ion transport, and morphogenesis. Of most interest is the downregulation of nuclear receptor proteins. Differentially expressed genes between early-stage cluster and late-stage clusters were identified. We found 90 genes preferentially overly expressed and 165 genes relatively downregulated at late-stage cancers. The advanced cancer appears differently from early-stage cancer in cell growth, cell adhesion, hormone activity, morphology, and cell–cell signaling compared with benign or early-stage cancer. Of particular interest are enzymes corresponding to pteridine biosynthesis, reported for the first time in this study. Real-time reverse transcription polymerase chain reaction showed that GCH1, KRT18, H3F3A, and MYBL2 were overly expressed in all cancer tissues, while MDFI, ARP3BETA, COL16A1, and MLN discriminated late-stage from early-stage cancers. Conclusion: The microarray provides valuable resources for comparing expression profiles of cancers at various stages and helps research the diagnosis and mechanism of ovarian cancer.

Objective: Uterine arteriovenous malformation (AVM) is a rare condition and can be life-threatening if not managed properly. We report a case that was diagnosed by typical ultrasound imaging and treated successfully with uterine arterial embolization. Case Report: A 28-year-old female, gravida 4, para 3, abortus 1, presented with massive vaginal bleeding 19 days after a termination of pregnancy due to fetal anomaly. After a dilatation and curettage 3 years previously, typical ultrasound image findings and a declining pattern of serum β-hCG (human chorionic gonadotrophin), acquired AVM was highly suspected. The patient underwent bilateral uterine arterial embolization. Four weeks later, there was nearly complete resolution of the AVM and the patient's menstrual cycle was restored 6 weeks after embolization. Conclusion: AVM can be diagnosed at an early stage with the aid of history taking and ultrasound. Percutaneous embolotherapy is a safe and effective treatment for AVM, especially when fertility preservation is desired.

Objective: We report a rare case of synchronous cancer consisting of ovarian endometrioid adenocarcinoma and endocervical mucinous adenocarcinoma. Related literature was reviewed and it appeared that no similar case had been reported previously. Case Report: A 30-year-old (gravida 1, para 1, abortus 0) woman complained of abdominal fullness, chest tightness and dyspnea on exertion of several days' duration. Gynecologic sonography showed a right complex adnexal cyst, 16 × 14 cm in size. Computed tomography showed an 18 × 16 cm right pelvic tumor, with both cystic and solid components, ascites and bilateral massive pleural effusion. Cytology of the pleural effusion showed no malignant cells. The patient underwent staging surgery. Histology showed moderately to poorly differentiated endometrioid adenocarcinoma of the right ovary with extensive lymphovascular permeation, as well as paraaortic and bilateral pelvic lymph node metastases. Extensive tumor thrombi were observed in the lymphovascular channels of the left ovary, bilateral tubes and uterus. Endocervical adenocarcinoma, < 3 mm in depth, was also identified on the cervix. The final surgical-pathologic stage of ovarian endometrioid adenocarcinoma was stage IIIc and of endocervical mucinous adenocarcinoma was stage IA1. Adjuvant chemotherapy with carboplatin and paclitaxel was prescribed postoperatively, but the malignancy was not controlled due to lung, brain and vulva metastases. The patient died of respiratory failure. Conclusion: The coexistence of primary neoplasms in the ovary and cervix is rare. Diagnosis should be based on histologic examination and requires appropriate treatment for both tumors.

Objective: Fetal tachyarrhythmia may cause fetal hydrops and lead to fetal morbidity and mortality. Supraventricular tachycardia and atrial flutter have been the most diagnosed. We present a case of fetal atrial flutter diagnosed during the second trimester treated with digoxin and sotalol and delivered at term. Case Report: A 30-year-old primigravid woman was diagnosed with fetal atrial flutter at the gestational age of 25 weeks with atrial rates of 480-520 bpm and ventricular rates of 200-250 bpm. Initially, she was treated with digoxin then with a combination of digoxin and sotalol. The fetal heart beat slowed after sotalol treatment but did not return to sinus rhythm. The fetus was delivered vaginally. Neonatal echocardiography showed a small apical ventricular septal defect and small patent ductus arteriosus. Electrocardiography also revealed atrial flutter with occasional atrial fibrillation. Conclusion: The efficacy of antiarrhythmic drug therapy for fetal atrial flutter has not been well established. In our case, we used sotalol combined with digoxin and the fetal heart beat slowed after therapy. Sotalol may be considered the drug of choice for fetal atrial flutter. If the fetal atrial flutter is resistant to these therapies, a combination of other congenital cardiac diseases or organic abnormalities should be considered.

Objective: Vulvar cancer is rare in Eastern females, especially in pre- and peripubertal girls. The prognosis of vulvar cancer is poor and treatment is variable. Case Report: A 14-year-old girl suffered from a left vulvar tenderness mass and underwent excision of the mass. The diagnosis of the pathology was vulvar yolk tumor with an embryonal carcinoma. After the vulvectomy, inguinal area lymph node dissection, chemotherapy (bleomycin, etoposide and cisplatin) treatment and radiotherapy, metastasis to lung was also noted after eight months. Resection of lung tumor was performed. She received chemotherapy with a combination of paclitaxel, ifosphamide and cisplatin (TIP) and received peripheral blood stem cell transplantation (PBSCT) twice and chemotherapy treatment of gemitabine and oxaliplatin (GEMOX). Up until now, the patient has been free of disease. Conclusion: High-dose TIP and GEMOX chemotherapy plus PBSCT for bone marrow rescues could be considered to treat patients with metastatic malignant vulvar germ cell tumor after failed first-line chemotherapy and radiation.

Objective: This study aimed to elucidate the possible relationship between surgical blood loss (SBL) and medical outcomes of laparoscopic-assisted vaginal hysterectomy (LAVH). Materials and Methods: Patients who underwent LAVH performed by the same surgeon for benign gynecologic diseases from 2004 to 2006 were analyzed retrospectively. Patients were divided into two groups according to the amount of SBL (< 150 mL or ≥ 150 mL, 75th percentile of mean SBL). Clinical medical outcomes of all women were analyzed to identify the effects of SBL during LAVH. Results: A total of 133 women with benign gynecologic disease were included. Group 1 (SBL < 150 mL) consisted of 108 patients and Group 2 (SBL≥ 150 mL) consisted of 25 patients. The mean operative time for patients with SBL≥ 150 mL was 36.1 minutes longer than that for patients with SBL < 150 mL (p < 0.001). Mean hospital stay, mean shift in serum hemoglobin, mean shift in serum hematocrit and mean flatulence relief time were not significantly different between the two groups. Conclusion: Greater SBL (≥ 150 mL) during LAVH was significantly associated with longer operating time, but had no detrimental effect on short-term surgical outcomes. Thus, efforts to minimize intraoperative bleeding and so reduce operative time will be beneficial for women undergoing LAVH.

Objective: Ovarian tumors are commonly encountered in clinical practice. Epithelial ovarian cancers account for the majority of female ovarian neoplasms. Some uncommon ovarian mucinous tumors have recently been termed “seromucinous” tumors because they exhibit both serous and mucinous features. Case Report: A 27-year-old female patient presented with a 2-month history of a palpable abdominal mass. Ultrasonography and computed tomography revealed a huge multilocular, solid pelvic cyst. Following staging surgery, pathological sections showed that the tumor was composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and undifferentiated cells. An ovarian seromucinous tumor was diagnosed. The neoplastic cells were located mainly within the ovarian epithelium with only focal stromal invasion. Metastatic implants were found in the pelvic peritoneum. The patient received six courses of chemotherapy after surgery and has been regularly followed. Conclusion: Seromucinous tumors can be classified from atypical proliferative tumors to invasive carcinomas. Death related to this kind of tumor is rare. The tumors are not common, and their clinical behavior is not as aggressive as other types. Prognostic factors have been studied, including morphologic cellular atypia, tumor necrosis, mitotic index, and depth of tumor invasion. Adjuvant therapy is necessary for patients with poor prognostic factors.

Electro-magnetic fields are everywhere in our life. The strength and duration of human exposure is proportional to the degree of industrialization. The possible health hazard has been investigated for decades. C. elegans (nematode) has been a sensitive tool to study aging and development. The current study investigated the possible effects of static magnetic fields (SMFs) on the developmental and aging processes of C. elegans. Nematodes were grown in the presence of SMFs of strengths varying from 0 to 200 mT. Treatment with a 200 mT SMF reduced the development times from L2 to young adult by approximately 20%. After SMF treatment, the average lifespan was reduced from 31 days to 25 days for wild-type nematodes. The up-regulation of genes associated with development and aging was verified by quantitative real-time RT-PCR. Nematodes carrying mutation in these genes also exhibited resistance to the SMFs treatment. Apparently, induction of gene expression is selective and dose-dependent. SMFs accelerate nematode development and shorten nematode lifespan through pathways associated with let-7, clk-1, unc-3, and age-1.

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). Conclusions: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Motivation: Ovarian cancer is the fifth leading cause of cancer deaths in women in the western world for 2013. In ovarian cancer, benign tumors turn malignant, but the point of transition is difficult to predict and diagnose. The 5-year survival rate of all types of ovarian cancer is 44%, but this can be improved to 92% if the cancer is found and treated before it spreads beyond the ovary. However, only 15% of all ovarian cancers are found at this early stage. Therefore, the ability to automatically identify and diagnose ovarian cancer precisely and efficiently as the tissue changes from benign to invasive is important for clinical treatment and for increasing the cure rate. This study proposes a new ovarian carcinoma classification model using two algorithms: a novel discretization of food sources for an artificial bee colony (DfABC), and a support vector machine (SVM). For the first time in the literature, oncogene detection using this method is also investigated. Results: A novel bio-inspired computing model and hybrid algorithms combining DfABC and SVM was applied to ovarian carcinoma and oncogene classification. This study used the human ovarian cDNA expression database to collect 41 patient samples and 9600 genes in each pathological stage. Feature selection methods were used to detect and extract 15 notable oncogenes. We then used the DfABC-SVM model to examine these 15 oncogenes, dividing them into eight different classifications according to their gene expressions of various pathological stages. The average accuracy of the eight classification experiments was 94.76%. This research also found some oncogenes that had not been discovered or indicated in previous scientific studies. The main contribution of this research is the proof that these newly discovered oncogenes are highly related to ovarian or other cancers. [ABSTRACT FROM AUTHOR]

Introduction: Resistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations. Methods: The lentiviral delivery system was used to upregulate or to suppress the expression of miR-21 in the human ovarian teratocarcinoma cell line PA1 and cell growth assays were used to monitor the expression of miR-21 at different time points. Antibodies directed toward CD133, a stem cell marker, were used to identify CSPCs in the PA1 cell population, and the level of miR-21 expression was determined in enriched CSPCs. Stem cell functional assays (sphere assay and assays for CD133 expression) were used to assess the effects of miR-21 on progression of the CD133+ population. Results: Knockdown of miR-21 in PA1 cells attenuated growth of PA1 cells whereas overexpression of miR-21 promoted cell growth. Moreover, knockdown of miR-21 resulted in a marked reduction in the CD133+ population and sphere formation of CSPCs. In contrast, overexpression of miR-21 resulted in a marked increase in the population of CD133+ cells as well as sphere formation of CSPCs. Conclusions: MicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells [ABSTRACT FROM AUTHOR]

The current study investigated the possible effects of static magnetic fields (SMFs) on the developmental and aging processes of Caenorhabdit!s elegans. Nematodes were grown in the presence of SMFs of strengths varying from 0 to 200mT. The rate of development and the lifespan were recorded. Treatment with a 200 mT SMF reduced the development time from the L2 to the L3 stage by 20%, from L3 to L4 by 23%, and from L4 to young adult by 31%. After SMF treatment, the average lifespan was reduced from 31 days to 24 days for wild-type nematodes. The up-regulation of clk-1, Iim-7, daf-2, unc-3 and age-1 after SMF treatment was verified by quantitative real-time RT-PCR. Apparently, induction of gene expression is selective and dose dependent. The total developmental time was significantly reduced for the Iin-4, lin-14, Iin-41 and Iim-7 mutants, but not for the Iet-7, clk-1, unc-3 and age-1 mutants. Lifespan analyses revealed that the let-7, unc-3 and age-1 mutants were not affected by SMF treatment. Here we show that SMF5 accelerate nematode development and shorten nematode lifespan through pathways associated with Iet-7, clk-1, unc-3 and age-1. [ABSTRACT FROM AUTHOR]

Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN) or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions. [ABSTRACT FROM AUTHOR]

The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles. [ABSTRACT FROM AUTHOR]

Background: An evidence-based initiation of quality improvement activity for reducing the usage of prophylactic antibiotic in laparoscopic-assisted vaginal hysterectomy (LAVH) in a tertiary hospital. Aims: The authors investigated whether single or multiple doses of cefazoline were more cost-effective in preventing postoperative infection associated with LAVH. Methods: The study groups comprised of 310 patients who had undergone LAVH continuously in a medical centre. Patients were divided into two groups on the basis of whether they received a single dose or multiple doses (range: two to four doses) of cefazoline during the perioperative period. Postoperative infections such as pelvic cellulitis or abscess, vaginal cuff abscess, wound infection and urinary tract infection that occurred either during hospitalisation or within one month after discharge were observed and recorded. Incremental cost-effectiveness ratio (ICER) was calculated using the mean direct drug cost and the prophylactic effect of infection in both groups. Results: The prophylactic effect of infection was similar in the single-dose group and the multiple-dose group (94.6% vs 93.9%, P = 0.986). The ICER was significantly lower in the single-dose group (153.3 vs 460.4, P < 0.001). Conclusions: The result revealed that a single dose of cefazoline is more cost-effective than multiple doses in the prevention of infection associated with LAVH. It fulfils the goal of cost minimisation and quality of care in today's environment of medical cost containment. [ABSTRACT FROM AUTHOR]

The suppressive effects of Camellia sinensis tea melanin (CSTM) on transformation of aryl hydrocarbon receptor (AhR) induced by 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) were disclosed for the first time. CSTM strongly inhibited TCDD-induced toxicity with IC50 equalling 20.4 μg mL−1. Daily administration of CSTM (40 mg kg−1, p.o.) prevented TCDD-induced body weight loss, ameliorated TCDD-induced mortality and prevented TCDD-induced hepatomegaly and thymic atrophy. Co-administration of CSTM significantly inhibited TCDD-induced hepatic CYP1 A1 activity. CSTM retarded transformation of AhR in vitro. In animals treated with CSTM, the antibody-secreting cells produced significantly ( P < 0.05) more antibodies (32–34%) than the antigen control. Administration of TCDD caused a suppression of antibody-forming cells of 29–33% against the antigen control level. Co-administration of CSTM restored immunity to the control level. We demonstrated that CSTM directly competed with TCDD during the transformation of AhR and suppressed the downstream activation of genes associated with TCDD toxicity. [ABSTRACT FROM AUTHOR]