Impact of rice GENERAL REGULATORY FACTOR14h (GF14h) on low-temperature seed germination and its application to breeding.

Direct seeding is employed to circumvent the labor-intensive process of rice (Oryza sativa) transplantation, but this approach requires varieties with vigorous low-temperature germination (LTG) when sown in cold climates. To investigate the genetic basis of LTG, we identified the quantitative trait locus (QTL) qLTG11 from rice variety Arroz da Terra, which shows rapid seed germination at lower temperatures, using QTL-seq. We delineated the candidate region to a 52-kb interval containing GENERAL REGULATORY FACTOR14h (GF14h) gene, which is expressed during seed germination.

Whole-genome analysis of recombinant inbred rice lines reveals a quantitative trait locus on chromosome 3 with genotype-by-environment interaction effects.

Elucidating genotype-by-environment interactions is fundamental for understanding the interplay between genetic and environmental factors that shape complex traits in crops. Genotype-by-environment interactions are of practical importance, as they determine the performance of cultivars grown in different environments, prompting the need for an efficient approach for evaluating genotype-by-environment interactions. Here, we describe a method for genotype-by-environment detection that involves comparing linear mixed models.

A Phase 2 Study of S-588410 Maintenance Monotherapy for Platinum-Treated Advanced or Metastatic Urothelial Carcinoma.

Background: Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy.

Objective: To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC.

Materials And Methods: This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression.

Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.

The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.

A prospective study to examine the accuracies and efficacies of prediction systems for response to neoadjuvant chemotherapy for muscle invasive bladder cancer.

The present study established systems to predict the chemo-sensitivity of muscle invasive bladder cancer (MIBC) for neoadjuvant chemotherapy (NAC) with methotrexate, vinblastine, doxorubicin plus cisplatin (M-VAC) and carboplatin plus gemcitabine (CaG) by analyzing microarray data. The primary aim of the study was to investigate whether the clinical response would increase by combining these prediction systems. Treatment of each MIBC case was allocated into M-VAC NAC, CaG NAC, surgery, or radiation therapy groups by their prediction score (PS), which was calculated using the designed chemo-sensitivity prediction system.

Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette-Guerin for patients with non-muscle invasive bladder cancer.

Purpose: A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC).

Materials And Methods: 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial.

Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer.

Cell division associated 1 (CDCA1) was screened as an oncogene that is overexpressed on several cancers, including prostate cancer. A highly immunogenic HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein was also identified. A phase I clinical trial was conducted for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination.

Effective induction of cytotoxic T cells recognizing an epitope peptide derived from hypoxia-inducible protein 2 (HIG2) in patients with metastatic renal cell carcinoma.

Purpose: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC.

Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan.

Background: To improve antitumor effects against metastatic renal cell carcinoma (mRCC), use of molecular target-based drugs in sequential or combination therapy has been advocated. In combination therapy, interferon (IFN)-α amplified the effect of sorafenib in our murine model (J Urol 184:2549, 2010), and cytokine-treated mRCC patients in Japan had good prognoses (Eur Urol 57:317, 2010). We thus conducted a phase II clinical trial of sorafenib plus IFN-α for untreated mRCC patients in Japan.

Relative and absolute risks of all-cause and cause-specific deaths attributable to atrial fibrillation in middle-aged and elderly community dwellers.

Background: The relative and absolute risks of outcomes other than all-cause death (ACD) attributable to atrial fibrillation (AF) stratified age have not been sufficiently investigated.

Methods: A prospective study of 23,634 community dwellers aged 40 years or older without organic cardiovascular disease (AF=335, non-AF=23,299) was conducted. Multivariate-adjusted rates, rate ratios (RRs) and excess deaths (EDs) for ACD, cardiovascular death (CVD) and non-cardiovascular death (non-CVD), and sex- and age-adjusted RR and ED in middle-aged (40 to 69) and elderly (70 years or older) for ACD, CVD, non-CVD, sudden cardiac death (SCD), stroke-related death (Str-D), neoplasm-related death (NPD), and infection-related death (IFD) attributable to AF were estimated using Poisson regression.

Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent mutations of UNC5C and prognostic importance of DNA repair gene mutations on survival.

Purpose: Because of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination of potential genetic drivers offers the possibility of improving therapeutic approaches and discovering novel prognostic indicators.

Experimental Design: Using pTN staging, we case-matched 81 patients with resected ≥pT2 bladder cancers for whom perioperative chemotherapy use and disease recurrence status were known. Whole-exome sequencing was conducted in 43 cases to identify recurrent somatic mutations and targeted sequencing of 10 genes selected from the initial screening in an additional 38 cases was completed.

Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.

Through genome-wide association analysis and an independent replication study using a total of 1131 bladder cancer cases and 12 558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P-value of 4.

Guidance for peptide vaccines for the treatment of cancer.

Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development.

Efficacy of everolimus in patients with advanced renal cell carcinoma refractory or intolerant to VEGFR-TKIs and safety compared with prior VEGFR-TKI treatment.

Objective: Everolimus is positioned as second-line treatment for metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated retrospectively the efficacy and safety of everolimus in Japanese patients with advanced renal cell carcinoma in the clinical setting.

Methods: Nineteen patients who discontinued treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors because of disease progression or adverse events were administered everolimus.

Outcome of metastasectomy for urothelial carcinoma: a multi-institutional retrospective study in Japan.

Purpose: We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma.

Materials And Methods: A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy.

High risks of all-cause and cardiovascular deaths in apparently healthy middle-aged people with preserved glomerular filtration rate and albuminuria: A prospective cohort study.

Background: The reason why coexistence of preserved estimated glomerular filtration rate (eGFR) and albuminuria contributes to a high risk of death and which cause of death increases all-cause mortality have not been elucidated.

Methods: A total of 16,759 participants aged 40 to 69 years with normal or mildly reduced eGFR (45-119 ml/min/1.73 m(2)) were enrolled and divided into six groups (group 1, eGFR: 90-119 without albuminuria; group 2, eGFR: 90-119 with albuminuria; group 3, eGFR: 60-89 without albuminuria (reference); group 4, eGFR: 60-89 with albuminuria; group 5, eGFR: 45-59 without albuminuria; group 6, eGFR: 45-59 with albuminuria) based on GFR estimated by using the CKD-EPI study equation modified by a Japanese coefficient and albuminuria (urine albumin-creatinine ratio ≥ 30 mg/g).

Impacts of clinicopathologic and operative factors on short-term and long-term survival in renal cell carcinoma with venous tumor thrombus extension: a multi-institutional retrospective study in Japan.

Background: Although the percentage of patients with renal cell carcinoma (RCC) extending into venous systems is unexpectedly high, the prognostic impact and independency of venous tumor thrombus-related factors on overall survival (OS) remain controversial. Furthermore, the prognostic impact of various clinicopathologic factors including tumor thrombus-related factors on OS may change with elapsed years after the intervention and also with follow-up duration of participants. The aim of the study is to explore independent and universal predictive preoperative and intraoperative clinicopathologic factors on OS in patients with RCC extending into venous systems using subgroup analysis in terms of restricted follow-up duration and yearly-based survivors.

Plasma low-molecular-weight proteome profiling identified neuropeptide-Y as a prostate cancer biomarker polypeptide.

In prostate cancer diagnosis, PSA test has greatly contributed to the early detection of prostate cancer; however, expanding overdiagnosis and unnecessary biopsies have emerged as serious issues. To explore plasma biomarkers complementing the specificity of PSA test, we developed a unique proteomic technology QUEST-MS (Quick Enrichment of Small Targets for Mass Spectrometry). The QUEST-MS method based on 96-well formatted sequential reversed-phase chromatography allowing efficient enrichment of <20 kDa proteins quickly and reproducibly.

Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in the bladder: a case report and review of the literature.

Background: Villous adenoma arising in the urinary tract is rare tumor. Most cases have been identified as benign neoplasm in the colon. Villous adenoma of the gastrointestinal tract is thought arise from premalignant polyps.

Comparison of predictability of future cardiovascular events between chronic kidney disease (CKD) stage based on CKD epidemiology collaboration equation and that based on modification of diet in renal disease equation in the Japanese general population--Iwate KENCO Study.

Background: Whether estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Study equation (eGFRCKDEPI) improves risk prediction compared to that calculated using the Modification of Diet in Renal Disease (MDRD) study equation (eGFRMDRD) has not been examined in a prospective study in Japanese people.

Methods And Results: Participants (n=24,560) were divided into 4 stages (1, ≥90; 2, 60-89 (reference); 3a, 45-59; 3b+ <45 ml·min(-1)·1.73 m(-2)) according to eGFRCKDEPI or eGFRMDRD.

Clear cell papillary cystadenocarcinoma of the epididymis: a case report and immunohistochemistry of markers for renal cell carcinoma.

Neoplasms of the epididymis are uncommon, and malignant tumors are extremely rare. We report a case of clear cell papillary cystadenocarcinoma of the epididymis presenting with a long history of painless scrotal mass on the left side. Immunohistochemical markers for clear cell renal cell carcinoma (RCC) were examined to distinguish between clear cell papillary cystadenocarcinoma of the epididymis and metastatic clear cell renal cell carcinoma.

Associations of marital status with mortality from all causes and mortality from cardiovascular disease in Japanese haemodialysis patients.

Background: Marital status is an important social factor associated with increased mortality from cardiovascular disease (CVD) and all causes. However, there has been no study on the association of marital status with mortality in haemodialysis patients.

Methods: We analysed data from a 5-year prospective cohort study of 1064 Japanese haemodialysis patients aged 30 years or older.

Neoadjuvant gemcitabine plus carboplatin for locally advanced bladder cancer.

Objective: Although cisplatin-based neoadjuvant chemotherapy followed by cystectomy was demonstrated to improve the survival among patients with locally advanced bladder cancer, its severe adverse events, including nephrotoxicity, are critical issues. We investigated the safety and activity of carboplatin, a mild nephrotoxic agent, combined with gemcitabine as a neoadjuvant chemotherapy compared with methotrexate, vinblastine, doxorubicin and cisplatin for patients with locally advanced bladder cancer.

Methods: We retrospectively evaluated 68 patients with locally advanced bladder cancer who received neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (n = 34) or gemcitabine and carboplatin (n = 34) followed by cystectomy at our institute.

Impact of four loci on serum tamsulosin hydrochloride concentration.

Tamsulosin hydrochloride is one of the most potent drugs for treatment of benign prostatic hyperplasia (BPH), however, the efficacy of tamsulosin hydrochloride varies among individuals. In this study, we measured the maximum serum concentration (Cmax) of tamsulosin hydrochloride in 182 of BPH patients and found remarkable individual variability. To investigate the genetic factors that regulate pharmacokinetics of tamsulosin hydrochloride, we conducted a genome-wide association study in these 182 BPH patients.