Analysis of mTOR Inhibition-Involved Pathway in Ovarian Clear Cell Adenocarcinoma

This study was designed to clarify the mechanism of the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1 (HIF-1) pathway using the cultured cell strain derived from human ovarian clear cell adenocarcinoma (CCA). Everolimus (a derivative of rapamycin)-treated cells and non-treated cells did not show any difference in mTOR expression. But, phosphorylated-mTOR (p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1 (p-4E-BP1), HIF-1α, and vascular endothelial growth factor (VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1α degradation system showed an increase in von-Hippel Lindau (VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1α by VHL and induction of apoptosis by cleaved caspase-3

Treatment Strategy for Recurrent and Refractory Epithelial Ovarian Cancer: Efficacy of High-Dose Chemotherapy with Hematopoietic Stem Cell Transplantation

According to population statistics in Japan, approximately 3,800 women die of ovarian ­cancer annually, and approximately 6,000 are affected by this disease. Ovarian cancer is ­referred to as a “silent tumor”, since patients have few subjective symptoms and by the time symptoms are observed, the cancer has progressed to Stage III or IV in about half of the patients. The basic treatment for advanced epithelial ovarian cancer is to remove as much of the tumor as possible, and subsequently to perform anticancer therapy using drugs such as cisplatin, carboplatin and paclitaxel, all of which have been shown to be effective for epi­thelial ovarian cancer. However, the 5-year survival rate in advanced ovarian cancer patients is still only about 20%, and a treatment that leads to long-term survival has yet to be developed. Here, we review the available treatments for ovarian cancer, and present the results of high-dose chemotherapy (HDC) performed in our hospital for recurrent and refractory ­ovarian cancer

Alterations in Mucin Expression in Ovarian Mucinous Tumors: Immunohistochemical Analysis of MUC2, MUC5AC, MUC6, and CD10 Expression

The aim of this study was to evaluate the immunohistochemical expression of MUC2, MUC5AC, MUC6, and CD10 in ovarian mucinous adenoma (MA), mucinous borderline tumor (MB), and mucinous adenocarcinoma (MC), and to analyze the relationship between prognosis and these expressions. The expression of MUC2, MUC5AC, MUC6, and CD10 was evaluated by immunohistochemical analysis in 29 cases of MA, 29 cases of MB, and 26 cases of MC and scored based on the percentage of positive cells. Moreover, the ovarian mucinous tumors were classified into 4 phenotypes based on the staining patterns: intestinal, gastrointestinal, gastric, and unclassified patterns. The gastrointestinal pattern and the expression of MUC2 and CD10 increased from MA to MC. Conversely, the gastric pattern and MUC5AC expression decreased from MA to MC. Low MUC2 expression in MC was correlated with a better long-term survival rate. MUC2 expression in MC may be a useful predictor of the clinical outcome. The expression patterns of MUC2, MUC5AC, MUC6, and CD10 indicated that intestinal metaplasia may arise from the gastric-like epithelium in MA and that a close association exists between carcinogenesis and intestinal metaplasia in major ovarian mucinous tumors

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

BackgroundVulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese.ObjectiveThe JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan.MethodsThe guideline was created according to the basic principles in creating the guidelines of JSGO.ResultsThe guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions.ConclusionOverall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases

Predicting perioperative venous thromboembolism in Japanese gynecological patients.

To develop a convenient screening method that can predict perioperative venous thromboembolism (VTE) and identify patients at risk of fatal perioperative pulmonary embolism (PE).Patients hospitalized for gynecological abdominal surgery (n = 183) underwent hematology tests and multidetector computed tomography (MDCT) to detect VTE. All statistical analyses were carried out using the SPSS software program (PASWV19.0J).The following risk factors for VTE were identified by univariate analysis: plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and prolonged immobility (all p<0.001); age, neoadjuvant chemotherapy (NAC), malignancy, hypertension, past history of VTE, and hormone therapy (all p<0.01); and hemoglobin, transverse tumor diameter, ovarian disease, and menopause (all p<0.05). Multivariate analysis using these factors revealed that PIC, age, and transverse tumor diameter were significant independent determinants of the risk of VTE. We then calculated the incidence rate of perioperative VTE using PIC and transverse tumor diameter in patient groups stratified by age. In patients aged ≤40 years, PIC ≥1.3 µg/mL and a transverse tumor diameter ≥10 cm identified the high-risk group for VTE with an accuracy of 93.6%. For patients in their 50 s, PIC ≥1.3 µg/mL identified a high risk of VTE with an accuracy of 78.2%. In patients aged ≥60 years, a transverse tumor diameter ≥15 cm (irrespective of PIC) or PIC ≥1.3 µg/mL identified the high-risk group with an accuracy of 82.4%.We propose new screening criteria for VTE risk that are based on PIC, transverse tumor diameter, and age. Our findings suggest the usefulness of these criteria for predicting the risk of perioperative VTE and for identifying patients with a high risk of fatal perioperative PE

Incidence rate of perioperative venous thromboembolism in patients groups stratified by age.

<p>Abbreviation: PIC, Plasmin-alpha2-plasmin inhibitor complex. Transverse, Transverse tumor diameter.</p

Results of multiple logistic regression analysis.

<p>Abbreviation: PIC, Plasmin-alpha2-plasmin inhibitor complex. Transverse, Transverse tumor diameter. SEM, Standard error of the mean (n = 183).</p