Rab3a and Rab27b Expression in Nonfunctioning Pituitary Adenomas

Patients with nonfunctioning pituitary adenoma (NFPA) have normal circulating levels of anterior pituitary hormones. Here we examined the expression of exocytic trafficking regulators, Rab27b and Rab3a, in surgically resected pituitary adenoma tissues by immunohistochemical (IHC) analysis using anti-Rab27b and anti-Rab3a antibodies. Among the examined tissues, just over half of the null-cell adenomas and one-third of the gonadotropin-producing adenomas were immunonegative for both Rab27b and Rab3a. However, no Rab-negative samples were observed among the functioning adenomas. These results suggested that downregulated Rab protein expression in anterior pituitary endocrine cells could underlie, at least in part, the hormone-secretion defects of nonfunctioning adenoma cells. Rab27b, Rab3a, and their cellular regulators might therefore be promising pathological markers of patients with NFPA

Relationship of Grade of Malignant Brain Tumor to Cancer Stem Cells and Survivin Expression

Glioblastoma (GBM) is difficult to completely cure by surgical treatment alone, and it is generally treated with a combination of surgery, radiotherapy, and chemotherapy. However, GBM is resistant to radiotherapy and chemotherapy, and complete cure cannot be achieved. Cancer stem cells (CSC) and survivin, which inhibit apoptosis, are considered as factors underlying tumor recurrence and the radiation- and drug-resistance of these tumors. We analyzed CSC and survivin expression in surgically excised specimens of malignant brain tumors to establish the relationships between the grades and CSC and survivin expression and between MIB-1 (Ki-67) expression and resistance. No relationship was noted between the grades and CSC or survivin expression, or between MIB-1 and CSC expression or between Grade 3 and 4 MIB-1 and survivin expression, although a correlation was noted between MIB-1 and survivin expression in Grade II tumors. These findings suggested that CSC are consistently contained in tumor tissue at a specific rate regardless of the histological grade, and the apoptosis of cells with low-level proliferative and cell cycling activities does not occur because these cells do not respond to chemotherapy or radiation, being resistant to treatment

Eribulin Treatment Induces High Expression of miR-195 and Inactivates the Wnt/β - catenin Signaling Pathway in Triple-negative Breast Cancer

Triple-negative breast cancer （TNBC） accounts for 10-15％ of all breast cancer cases and shows a poor prognosis with 30％ distant metastasis. With few specific target molecules and ineffective hormonal and anti-HER2 treatment, an alternative therapeutic method for TNBC is urgently required. Recently, a non-taxane inhibitor of microtubule dynamics called eribulin was developed for breast cancer therapy. Eribulin induces irreversible mitotic mass formation in cancer cells during the G2-M phase, initiating apoptosis; however, the mechanism underlying this eribulin activity remains unclear. We reported previously that exposing non-basal-like （NBL） TNBC cells to eribulin increases miR-195 expression, which in turn decreases the expression of targeted Wnt3a. The present study sought to further clarify the mechanism of this antitumor effect by exploring how eribulin affects Wnt/β - catenin signaling based on miRNA expression changes in TNBC. In an NBL type of human breast cancer cell line （MDA-MB-231 cells）, we compared the expression levels of Wnt/β catenin signaling pathway proteins in cells exposed to an miR-195 mimic （cells transfected with miR-195 and in which Wnt3a expression was suppressed） and in cells exposed to eribulin. Expression levels of Wnt3a, β -catenin, and GSK-3β were measured by ELISA and observed by fluorescence immunostaining. Wnt3a and β -catenin expression was significantly lower and GSK-3β expression was significantly higher in the cells exposed to eribulin and transfected with miR-195 mimic than in the untreated controls, suggesting that eribulin inactivates the Wnt/β -catenin signaling pathway. Therefore, a novel antitumor mechanism of eribulin was determined, whereby eribulin induces high expression of miR-195 to inactivate the Wnt/β -catenin signaling pathway in NBL-type TNBC

Protocol for a multicentre, prospective, cohort study to investigate patient satisfaction and quality of life after immediate breast reconstruction in Japan: the SAQLA study

Introduction The aim of breast reconstruction (BR) is to improve patients' health-related quality of life (HRQOL). Therefore, measuring patient-reported outcomes (PROs) would clarify the value and impact of BR on a patient's life and thus would provide evidence-based information to help decision-making. The Satisfaction and Quality of Life After Immediate Breast Reconstruction study aimed to investigate satisfaction and HRQOL in Japanese patients with breast cancer who undergo immediate breast reconstruction (IBR). Methods and analysis This ongoing prospective, observational multicentre study will assess 406 patients who had unilateral breast cancer and underwent mastectomy and IBR, and were recruited from April 2018 to July 2019. All participants were recruited from seven hospitals: Okayama University Hospital, Iwate Medical University Hospital, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Showa University Hospital, University of Tsukuba Hospital, Osaka University Hospital and Yokohama City University Medical Center. The patients will be followed up for 36 months postoperatively. The primary endpoint of this study will be the time-dependent changes in BREAST-Q satisfaction with breast subscale scores for 12 months after reconstructive surgery, which will be collected via an electronic PRO system. Ethics and dissemination This study will be performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare, the modified Act on the Protection of Personal Information and the Declaration of Helsinki. This study protocol was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, on 2 February 2018 (1801-039) and all other participating sites. The findings of this trial will be submitted to an international peer-reviewed journal

Occurrence of equine coital exanthema (ECE) in stallions in Japan and effectiveness of treatment with valacyclovir for ECE

Equine coital exanthema (ECE) has been reported in many countries, but equine herpesvirus 3 (EHV-3) has been isolated only once in Japan. In 2015, symptoms of ECE were found, and EHV-3 was isolated in two stallions. Valacyclovir, an anti-herpesvirus agent, was administered orally. The stallions rested from mating for more than two weeks, causing enormous financial losses because of their high fees. This is the first study in which valacyclovir was administered for ECE. Though valacyclovir treatment did not shorten the duration of healing, the affected area did not expand after administration of valacyclovir. Valacyclovir therefore seems to be effective for suppression of EHV-3 infection. Further investigation about the administration protocol might be required

BRCA1 mutated cells are less likely to undergo ROS-mediated apoptosis after exposure to eribulin and paclitaxel

Triple negative breast cancer has a high frequency of BRCA1 gene mutations. In this experiment, we examined whether there are cells that are not led to apoptosis in different subtypes of breast cancer with poor prognosis with BRCA1 mutation and wild type BRCA cells. Cells with BRCA1 wild-type （MDA-MB-231 and BT-549） or mutated （MDA-MB-436）BRCA1 were exposed to anticancer drugs, and the levels of reactive oxygen species （ROS）produced by oxidative stress and Annexin V （an index of apoptosis） were examined. The wild-type MDA-MB-231 cells showed increased ROS levels and Annexin V after exposure to eribulin and paclitaxel. Hence, the pathway leading to apoptosis may be activated by oxidative stress. ROS levels in BT-549 cells were significantly increased after exposure to eribulin and paclitaxel. However, there was no change in Annexin V. BRCA1-mutated MDA-MB-436 cells showed significantly increased ROS levels after exposure to eribulin and paclitaxel and no change in the Annexin V levels. This suggests that BRCA1 wild-type BT-549 cells and BRCA1-muted MDA-MB-436 cells were resistant to ROS-mediated apoptosis. These results indicate that BRCA1 mutation and cell subtypes should be investigated prior to selecting the chemotherapy combination to enable appropriate selection in clinical practice

Period of excretion of equine herpesvirus 3 (EHV-3) from a stallion before showing clinical signs of equine coital exanthema and the effect of acyclovir treatment on the duration of EHV-3 excretion

In 2017, two Thoroughbred stallions, A and B in Farms A and B, respectively, in Hokkaido in Japan showed clinical signs of equine coital exanthema (ECE). In 2020, stallion C in Farm B showed clinical signs of ECE. Eighteen mares were mated within five days before stallion A developed ECE. Ten mares that mated within 3 days before onset showed clinical signs of ECE on the external genitalia. Equine herpesvirus 3 (EHV-3) was isolated from vaginal swabs from three mares that mated within 2 days before onset. Swabs from 12 mares that mated within 4 days before onset were real-time PCR (rPCR)-positive and nine of those mares had an increased EHV-3 antibody titer. The three stallions were administered valaciclovir orally and topical acyclovir ointment was applied. Treatment started on the next day after onset in stallion A and on the day of onset in stallions B and C. EHV-3 was firstly isolated from penis swabs of stallions A and B before treatment and from penis swabs of stallion C 2 days after treatment. EHV-3 was not isolated after 8, 5 and 8 days from onset in stallions A, B and C, respectively. However, swabs were rPCR-positive for at least 12, 9 and 15 days after onset of stallions A, B and C, respectively. EHV-3 was excreted from the stallions at least within 4 days before the onset of ECE, and acyclovir treatment resulted in the termination of excretion within 8 days after onset