MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1

<p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) is the key process driving cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce EMT in cancer cells. Recent studies have implied that noncoding microRNAs (miRNAs) act as crucial modulators for EMT. The aims of this study was to determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and the possible role of miRNA in controlling BMI-1 expression.</p> <p>Methods and results</p> <p>We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and detected a strong association with invasive capability. Stable silencing of BMI-1 in invasive mesenchymal-type EC cells up-regulated the epithelial marker E-cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced cell invasion <it>in vitro</it>. Furthermore, we discovered that the expression of BMI-1 was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region 3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to epithelial transition (MET) by restoring E-cadherin, reducing Vimentin expression, and inhibiting cell invasion <it>in vitro</it>. Moreover, BMI-1 knockdown inhibited <it>in vitro </it>EC cell proliferation and clone growth, correlated with either increased p16 expression or decreased expression of stem cell and chemoresistance markers (SOX-2, KLF4 and MRP-1).</p> <p>Conclusion</p> <p>These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.</p

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

Current status of tertiary debulking surgery and prognosis after secondary debulking surgery for recurrent Müllerian epithelial cancer in Japan: a retrospective analysis of 164 patients (KCOG-G1402)

BackgroundThis study aimed to evaluate the current status of secondary debulking surgery (SDS) and tertiary debulking surgery (TDS; performed for recurrence after SDS) and to assess the overall survival after recurrence of Müllerian epithelial cancer in Japan. We also evaluated the data of patients who underwent a fourth debulking surgery (i.e., quaternary debulking surgery (QDS)).MethodsWe conducted a retrospective study of 164 patients with recurrent Müllerian epithelial cancers (i.e., ovarian, tubal, and peritoneal cancers). The SDS was performed between January 2000 and September 2014 in 20 Japanese hospitals. Clinicopathological data were collected and analyzed.ResultsOf the 164 patients, 66 patients did not have a recurrence or died after SDS. Ninety-eight patients had a recurrence after SDS. Forty-three of the 98 patients underwent TDS; 55 of the 98 patients did not undergo TDS and were classified into the non-TDS group. The overall survival (OS) after SDS was significantly better in the TDS group than in the non-TDS group. The median OS after SDS was 123 and 42 months in the TDS group and non-TDS group, respectively. Of the 43 patients who received TDS, 11 patients were further treated with QDS. The median OS after SDS was 123 months for patients who underwent QDS.ConclusionsThis multicenter study on the prognosis of post-SDS is apparently the first report on QDS in Japan. Patients undergoing TDS have a good prognosis, compared to patients in the non-TDS group. Novel drugs are being evaluated; however, debulking surgery remains a necessary treatment for recurrence

Nerve-Sparing Radical Hysterectomy Using the Okabayashi-Kobayashi Method

Radical hysterectomy (RH) is a standard treatment for early-stage cervical cancer. This surgery extirpates the uterus along with the paracervical tissues, vagina, and the paracolpium to achieve local control. Pelvic lymphadenectomy is a critical component of RH performed for regional control. A clear understanding of pelvic anatomy is critical to safely performing a RH and achieving optimal oncological and functional outcomes. The various surgical steps can damage the pelvic autonomic nerves, and a systematic nerve-sparing technique is used for the preservation of autonomic nerves. There is an intricate vascular network in the lateral paracervix (cardinal ligament) and the pelvic sidewall. We need to comprehend the three-dimensional structure of the vascular and nerve anatomy in the pelvis to perform RH effectively and safely. We can create six spaces around the uterine cervix, including the paravesical spaces, pararectal spaces, a vesicovaginal space, and a rectovaginal space to reveal the target of extirpation. It is critical to find the proper tissue plane separated by the layers of membranous connective tissue (fascia), in order to minimize intraoperative bleeding

Risk of cerebral palsy associated with neonatal encephalopathy in macrosomic neonates

Aim To determine whether macrosomic infants with a birthweight of 4.0kg or more have increased risk of cerebral palsy associated with neonatal encephalopathy (Enc-CP). Methods A retrospective review of 132 singleton infants with Enc-CP fulfilling all of the following criteria: born at gestational week (GW) 37 or more (n=126) or weighing 2.5kg or more at birth (n=116) in or after January 2009 in Japan; no identifiable causes of cerebral palsy other than antenatal or intrapartum hypoxia; and exhibition of neonatal encephalopathy. National statistics of Japan were used to determine the numbers of infants according to birthweight categories. Results Of the 116 infants with a birthweight of 2.5kg or more, 46 (39.7%), 49 (42.2%), 17 (14.7%) and four (3.4%) infants had birthweights of 2.5-2.99, 3.0-3.49, 3.5-3.99 and 4.0kg or more, respectively. Corresponding figures among Japanese infants born in 2009-2011 were 42.8%, 45.4%, 10.9% and 0.90%, respectively. Infants with a birthweight of 4.0kg or more had a relative risk (95% confidence interval) of Enc-CP of 3.89 (1.52-9.95) compared to those with a birthweight of 2.5-2.99kg. Conclusion Japanese infants with a birthweight of 4.0kg or more have increased risk of Enc-CP

Impact of FDG PET in optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer

Purpose To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer. Methods A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces). Results Of the 89 PET scans, 52 (58.4 %) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2 % of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was = 12 months had such disease (P = 0.0031). Conclusion PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of >= 12 months are the best candidates for cytoreductive surgery

Clinicopathological characteristics and prognostic factors of ovarian granulosa cell tumors : A JSGO-JSOG joint study

Objectives. The aim of this study was to elucidate the clinicopathological features of ovarian granulosa cell tu-mors (GCTs) and to identify the prognostic factors. Methods. The Japanese Society of Gynecologic Oncology (JSGO) conducted an observational retrospective co-hort study of women with GCTs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology (JSOG) between 2002 and 2015. Clinicopathological features, including lymph node metastasis, were evaluated. In addition, we performed a prognostic analysis of patients between 2002 and 2011 for whom survival data were available. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed. Results. We identified 1426 patients with GCTs. Of the 222 patients who underwent lymph node dissection, 10 (4.5%) had lymph node metastasis. The incidence of lymph node metastasis in patients with pT1, pT2, and pT3 was 2.1%, 13.3%, and 26.7%, respectively (p < 0.001). Prognostic analysis was performed on 674 patients. In the multivariate Cox regression analysis, residual disease after initial surgery (hazard ratio (HR) = 10.39, 95% confidence interval (CI) = 3.15-34.29) and lymph node metastasis (HR = 5.58, 95% CI = 1.62-19.19) were independent risk factors for cancer-specific survival. Conclusions. In the initial surgery for GCTs, lymph node dissection can be omitted if the operative finding is pT1. In cases of pT2 or higher, lymph node dissection should be considered. Debulking is critical for achieving no gross residual tumor at the end of the surgery. (c) 2021 Elsevier Inc. All rights reserved