Japanese nationwide observational multicenter study of tumor BRCA1/2 variant testing in advanced ovarian cancer.

The association between germline BRCA1 and BRCA2 pathogenic variants (mutations: gBRCAm) and ovarian cancer risk is well established. Germline testing alone cannot detect somatic BRCA1/2 pathogenic variants (sBRCAm), which is calculated based on the proportion of tumor BRCAm (tBRCAm) from tumor samples and gBRCAm. Homologous recombination deficiency (HRD) results mainly from genetic/epigenetic alterations in homologous recombination repair-related genes and can be evaluated by genomic instability status.

Survival and reproductive outcomes after fertility-sparing surgery performed for borderline epithelial ovarian tumor in Japanese adolescents and young adults: Results of a retrospective nationwide study.

Objective: Epithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression-free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility-sparing surgery (FSS). We conducted a Japan-wide study to understand post-FSS prognosis in relation to clinical characteristics and types of FSS performed.

Cellular and Humoral Immune Responses Induced by an HLA Class I-restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer.

The HLA-A*24:02-restricted peptide vaccine targeting Wilms' tumor 1 (WT1) (WT1 vaccine) is a promising therapeutic strategy for ovarian cancer; however, its efficacy varies among patients. In this study, we analyzed WT1-specific immune responses in patients with advanced or recurrent ovarian cancer that was refractory to standard chemotherapies and their associations with clinical outcomes. In 25 patients, the WT1 vaccine was administered subcutaneously weekly for 3 months and biweekly thereafter until disease progression or severe adverse events.

The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study.

Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan - OCEAN (Osaka Clinical resEArch of HPV vacciNe) study - to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old.

Minimizing abdominal incision for transverse uterine fundal incision by aspiration of amniotic fluid and reduction of uterine size.

Aim: Transverse uterine fundal incision (TUFI) was developed to avoid catastrophic hemorrhage associated with cesarean section of the placenta previa-accreta. Abdominal incisions extend as far as the upper abdomen in patients in the third trimester of pregnancy and require general anesthesia. Instead, we tried to aspirate amniotic fluid (AF) to reduce the uterine size.

Value and limitation of conization as a diagnostic procedure for cervical neoplasm.

Aim: In the recent years, the number of cervical conization procedures performed for diagnostic or therapeutic purposes is increasing, accompanied by increased cervical neoplasia among young women. This study aimed to analyze the clinical data of patients who underwent conization in Japan.

Methods: Among the 14 832 cases of conization registered in 205 facilities over 2 years (2009-2011), the data of 2409 and 12 417 patients who underwent conization for diagnostic and therapeutic purposes, respectively, were retrospectively analyzed.

Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patients report for 2015 and annual treatment report for 2010.

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2015 and the Annual Treatment Report for 2010 on the outcomes of patients who started treatment in 2010.

Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment was initiated in 2015 were analyzed retrospectively.

A Japanese survey of malignant disease in pregnancy.

Background: In recent years, the incidence of malignant disease in pregnancy has been increasing, but there are few large-scale surveys of malignant disease in pregnancy in Japan. The aim of this study was to survey malignant disease occurring during pregnancy in Japan.

Methods: Malignant disease in pregnancy was defined as diagnosis or treatment for malignant disease, except in situ carcinoma during pregnancy, or within 1-year postpartum.

Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications.

Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2-D monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3-D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals.

Single-dose intra-arterial neoadjuvant chemotherapy while waiting for radical hysterectomy for stage IB-IIB cervical cancer.

Extended wait time prior to initial surgery may increase patients' anxiety. Therefore, patients may opt to receive other available treatments to inhibit tumor growth until surgery. This retrospective study describes our experience with single-dose intra-arterial neoadjuvant chemotherapy (IANAC) to more effectively utilize the wait time prior to radical hysterectomy.

CpG oligodeoxynucleotides potentiate the antitumor activity of anti-BST2 antibody.

Numerous monoclonal antibodies (mAb) targeting tumor antigens have recently been developed. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) via effector cells such as tumor-infiltrating natural killer (NK) cells and macrophages are often involved in mediating the antitumor activity of mAb. CpG oligodeoxynucleotides (ODN) have a potent antitumor activity and are considered to increase tumor infiltration of NK cells and macrophages.

Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset Chronic Kidney Disease in the Japanese General Population.

Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate <60 mL/min per 1.

Annexin A4 induces platinum resistance in a chloride-and calcium-dependent manner.

Platinum resistance has long been a major issue in the treatment of various cancers. We previously reported that enhanced annexin A4 (ANXA4) expression, a Ca2+-regulated phospholipid-binding protein, induces chemoresistance to platinum-based drugs. In this study, we investigated the role of annexin repeats, a conserved structure of all the annexin family, responsible for platinum-resistance as well as the effect of knockdown of ANXA4.

New-onset hypertension and risk for chronic kidney disease in the Japanese general population.

Objectives: Our aims were to assess the progression rate of normotension and prehypertension to hypertension in Japan, and the effect of the new-onset hypertension on chronic kidney disease (CKD).

Methods: This was a nationwide study of 45 378 Japanese aged 40-74 years (mean age 60 years, 37% men) without hypertension or cardiovascular disease at baseline. At baseline and 3-year follow-up, blood pressure (BP) and kidney function were assessed.

Rapid detection of causative pathogen of peritonitis using in-situ hybridization in a patient with continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) peritonitis is a common problem in patients on peritoneal dialysis, and the bacteriological diagnosis is important for the treatment of this condition. We used Hybrizep (a method for detecting the genes of bacteria ingested in phagocytes), to detect the causative bacterium in a 50-year-old woman receiving peritoneal dialysis who was admitted our hospital with bacterial peritonitis. The test, using peritoneal dialysis fluid, was positive for Streptococcus epidermidis.

Rhabdomyolysis after simvastatin therapy in an HIV-infected patient with chronic renal failure.

We encountered a 49-year-old HIV-infected man with chronic renal insufficiency who developed rhabdomyolysis after treatment with simvastatin. He recovered after initiating hemodialysis and discontinuing oral medications. Rhabdomyolysis most likely resulted from an excessive blood concentration of simvastatin caused by concomitant use of fluconazole in the presence of renal insufficiency.

Serum cystatin C reliably detects renal dysfunction in patients with various renal diseases.

A clinical investigation was conducted to clarify the reliability and efficacy of serum cystatin C measurement for estimation of the glomerular filtration rate (GFR). Two hundred twelve patients with various renal diseases enrolled in the study. All patients were evaluated for 24-hour creatinine clearance (24 h C(Cr)) and the standard sodium thiosulfate clearance test (C(Thio)) within a week of blood sample collection.

Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure.

Skeletal resistance to parathyroid hormone (PTH) is one of the major abnormalities underlying bone diseases in uremia, the mechanism of which has not yet been fully elucidated. Osteoclastogenesis inhibitory factor (OCIF), or osteoprotegerin, is a natural decoy receptor for osteoclast differentiation factor (ODF), produced by osteoblasts in response to PTH. To elucidate the kinetics and roles of OCIF in chronic renal failure, serum OCIF levels were measured in 46 predialysis patients and 21 dialysis patients by means of enzyme-linked immunosorbent assay (ELISA).

Cancer immunogene therapy.

The establishment of cancer in a host involves at least two major events: the escape of tumor cells from normal growth control and their escape from immunological recognition. Because of this nature of their development, cancer cells seem to be predominatly poorly immunogenic. In contrast to the previous idea that cancer cells express no recognizable antigens, recent progress in the identification and characterization of tumor antigens, as well as the expansion of knowledge on the cellular and molecular mechanisms of antigen recognition by the immune system, have raised the possibility of using immunotherapy to treat certain tumors.

CD40 ligand promotes priming of fully potent antitumor CD4(+) T cells in draining lymph nodes in the presence of apoptotic tumor cells.

The presence or absence of CD4(+) T cell help can determine the direction of adaptive immune responses toward either cross-priming or cross-tolerance. It has been demonstrated that interactions of CD40-CD40 ligand can replace CD4(+) T cell help and enable dendritic cells to prime cytotoxic T cells. Here, we demonstrate that antitumor reactivity induced in regional lymph nodes (LNs) by s.

Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy.

Objective: In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of pIgR in the patients with and without IgAN.

Subjects And Methods: Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as A1 and A2 with and without Pvu II site, respectively.