Search

Purpose: To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion., Methods: We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3 months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function., Results: Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n = 164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001)., Conclusions: Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

Background: Neutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC)., Patients and Methods: This study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy., Results: Sixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia., Conclusion: Age and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma., Methods: A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan-Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses., Results: Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161-3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632., Conclusion: The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy., (© 2016 The Japanese Urological Association.)

Purpose: To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC)., Methods: We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC., Results: The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC., Conclusions: Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.

Background: To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP)., Methods: We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 < PV < 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72)., Results: Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3., Conclusions: A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Protein phosphatase 2A (PP2A) is an enzyme useful for detecting several natural toxins represented by okadaic acid and microcystins. We found that the production of the recombinant human PP2A catalytic subunit (rhPP2Ac) in High Five insect cells could markedly increase when the cells were cultured at 19 °C instead of 27 °C used under conventional conditions. The yield and purity of the enzyme increased four- and three-folds, respectively. The benefit of the altered culturing temperature was observed with the recombinant human protein phosphatase 2B but not 2Cα. The different responses among the enzymes suggest the involvement of an enzyme-specific mechanism that leads to the catalytic subunit overexpression. This is the first report to produce rhPP2Ac at a temperature lower than that used under conventional culture conditions (27 °C) used in the baculovirus expression system with High Five insect cells.

Physical dormancy of seed is an adaptive trait that widely exists in higher plants. This kind of dormancy is caused by a water-impermeable layer that blocks water and oxygen from the surrounding environment and keeps embryos in a viable status for a long time. Most of the work on hardseededness has focused on morphological structure and phenolic content of seed coat. The molecular mechanism underlying physical dormancy remains largely elusive. By screening a large number of Tnt1 retrotransposon-tagged Medicago truncatula lines, we identified nondormant seed mutants from this model legume species. Unlike wild-type hard seeds exhibiting physical dormancy, the mature mutant seeds imbibed water quickly and germinated easily, without the need for scarification. Microscopic observations of cross sections showed that the mutant phenotype was caused by a dysfunctional palisade cuticle layer in the seed coat. Chemical analysis found differences in lipid monomer composition between the wild-type and mutant seed coats. Genetic and molecular analyses revealed that a class II KNOTTED-like homeobox (KNOXII) gene, KNOX4, was responsible for the loss of physical dormancy in the seeds of the mutants. Microarray and chromatin immunoprecipitation analyses identified CYP86A, a gene associated with cutin biosynthesis, as one of the downstream target genes of KNOX4 This study elucidated a novel molecular mechanism of physical dormancy and revealed a new role of class II KNOX genes. Furthermore, KNOX4-like genes exist widely in seed plants but are lacking in nonseed species, indicating that KNOX4 may have diverged from the other KNOXII genes during the evolution of seed plants.

Background: To identify preoperative predictive factors for biochemical recurrence (BCR) and to further stratify its risk in high-risk localized prostate cancer patients receiving radical prostatectomy (RP)., Methods: Subjects included 195 high-risk prostate cancer patients undergoing RP from 2000 to 2012. RP consisted of retropubic radical prostatectomy and robot-assisted radical prostatectomy, involving 84 cases and 111 cases, respectively. BCR was defined as a prostate serum antigen (PSA) level ≥0.2 ng/mL. BCR-free survival (BCRFS) was calculated using the Kaplan-Meier method. Preoperative predictors of BCR were assessed with Cox's proportional hazard regression analysis., Results: Eighty-nine patients (45.6 %) experienced recurrence. BCRFS rates 3 and 5 years after RP were 58 and 50 %, respectively. Prostate volume, transition zone volume, and Gleason score were not significantly associated with BCR. Patients with higher preoperative PSA, PSA density (PSAD), PSA density of the transition zone, percentage of positive cores (PPC), and PPC from the dominant side showed significantly lower BCRFS. The PPC from the dominant side and PSAD were significant independent prognostic factors for BCR. Using these variables, the hazard ratio of BCR could be calculated and patients stratified into three risk groups. The 5-year BCRFS rates for Groups 1, 2, and 3 were 64.9 %, 48.1 %, and 21.3 %, respectively., Conclusions: Patients with high-risk localized prostate cancer as currently defined do not have uniformly poor prognosis after RP. PPC from the dominant side and PSAD are significant predictors of BCR. These factors can identify high-risk patients with very poor prognosis.

The purpose of the present study was to evaluate the wear of four different ceramics and human enamel. The ceramics used were lithium disilicate glass (e.max Press), leucite-reinforced glass (GN-Ceram), yttria-stabilized zirconia (Aadva Zr), and feldspathic porcelain (Porcelain AAA). Hemispherical styli were fabricated with these ceramics and with tooth enamel. Flattened enamel was used for antagonistic specimens. After 100,000 wear cycles of a two-body wear test, the height and volume losses of the styli and enamel antagonists were determined. The mean and standard deviation for eight specimens were calculated and statistically analyzed using a non-parametric (Steel-Dwass) test (α = 0.05). GN-Ceram exhibited greater stylus height and volume losses than did Porcelain AAA. E.max Press, Porcelain AAA, and enamel styli showed no significant differences, and Aadva Zr exhibited the smallest stylus height and volume losses. The wear of the enamel antagonist was not significantly different among GN-Ceram, e.max Press, Porcelain AAA, and enamel styli. Aadva Zr resulted in significantly lower wear values of the enamel antagonist than did GN-Ceram, Porcelain AAA, and enamel styli. In conclusion, leucite-reinforced glass, lithium disilicate glass, and feldspathic porcelain showed wear values closer to those for human enamel than did yttria-stabilized zirconia., (© 2016 Eur J Oral Sci.)

The aim of this study was to investigate the association between serum total cholesterol (TC) level and biochemical recurrence (BCR) following radical prostatectomy (RP). The study included 562 patients with T1-3N0M0 prostate cancer, who underwent RP at our institution between 2002 and 2010. No patients received neoadjuvant and/or adjuvant therapy. The associations between preoperative TC level, clinicopathological factors and BCR were assessed using univariate and multivariate analyses. During follow-up (mean, 54.0 months), 168 patients (168/562, 29.9%) experienced BCR, with a 5-year BCR-free rate of 67.2%. Of the clinicopathological characteristics investigated, statin use and lymphovascular invasion (LVI) status were associated with lower TC level (P=0.003 and P=0.014, respectively). In the univariate analysis, a higher serum prostate-specific antigen (PSA) level at diagnosis, extracapsular extension, positive surgical margin, seminal vesicle invasion, LVI, perineural invasion, higher Gleason score (GS ≥8) based on the RP specimen, increased body mass index, and low preoperative TC level, were significantly associated with BCR. In the multivariate analysis, the TC level was an independent predictor of BCR (hazard ratio = 0.925 per 10 mg/dl; 95% confidence interval: 0.879-0.973; P=0.003), as was the serum PSA level, extracapsular extension, positive surgical margin and the GS. Low preoperative serum TC levels were associated with an increased risk of BCR among prostate cancer patients who underwent RP. Our findings suggest that the preoperative serum TC level may provide important clinical information that may prove to be useful in patient counseling.

The symbiosis between leguminous plants and soil rhizobia culminates in the formation of nitrogen-fixing organs called nodules that support plant growth. Two Medicago truncatula Tnt1-insertion mutants were identified that produced small nodules, which were unable to fix nitrogen effectively due to ineffective rhizobial colonization. The gene underlying this phenotype was found to encode a protein containing a putative membrane-localized domain of unknown function (DUF21) and a cystathionine-β-synthase domain. The cbs1 mutants had defective infection threads that were sometimes devoid of rhizobia and formed small nodules with greatly reduced numbers of symbiosomes. We studied the expression of the gene, designated M truncatula Cystathionine-β-Synthase-like1 (MtCBS1), using a promoter-β-glucuronidase gene fusion, which revealed expression in infected root hair cells, developing nodules, and in the invasion zone of mature nodules. An MtCBS1-GFP fusion protein localized itself to the infection thread and symbiosomes. Nodulation factor-induced Ca(2+) responses were observed in the cbs1 mutant, indicating that MtCBS1 acts downstream of nodulation factor signaling. MtCBS1 expression occurred exclusively during Medicago-rhizobium symbiosis. Induction of MtCBS1 expression during symbiosis was found to be dependent on Nodule Inception (NIN), a key transcription factor that controls both rhizobial infection and nodule organogenesis. Interestingly, the closest homolog of MtCBS1, MtCBS2, was specifically induced in mycorrhizal roots, suggesting common infection mechanisms in nodulation and mycorrhization. Related proteins in Arabidopsis have been implicated in cell wall maturation, suggesting a potential role for CBS1 in the formation of the infection thread wall., (© 2016 American Society of Plant Biologists. All Rights Reserved.)

Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

PTEN (phosphatase and tensin homologue) is the first tumor suppressor identified to have phosphatase activity and its gene is the second most frequently deleted or mutated tumor-suppressor gene associated with human cancers. Germline PTEN mutations are the cause of three inherited autosomal dominant disorders. Phosphatidylinositol 3,4,5,-triphosphate (PIP3), the product of the PI3 kinase, is one of the key intracellular targets of PTEN's phosphatase activity, although PTEN's phosphatase-independent activities have also been identified. PTEN is critical for stem cell maintenance, which contributes to its controlled tumorigenesis. PTEN loss leads the development of cancer stem cells (CSCs) that share properties with somatic stem cells, including the capacity for self-renewal and multi-lineage differentiation. Methods to isolate and functionally test stem cells and CSCs are important for understanding PTEN functions and the development of therapeutic approaches to target CSCs without having adverse effects on normal stem cells. Here, we describe protocols for the isolation and functional analysis of PTEN deficient embryonic stem cells, hematopoietic stem cells and leukemia-initiating cells (LICs), neural stem cells, and prostate stem cells and CSCs.

Objectives: The aim of this study was to investigate the effect of positive surgical margin (PSM) without extraprostatic extension after robot-assisted radical prostatectomy (RARP)., Materials and Methods: We retrospectively reviewed 837 patients who underwent RARP for clinically localized prostate cancer without neoadjuvant endocrine therapy. The pT2+category lesions were defined according to World Health Organization classification. The actuarial probabilities of biochemical recurrence-free survival (BCR-FS) were determined using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazards regression analyses were also used to identify independent predictors for BCR., Results: Of the 837 patients, 102 (12.2%) experienced BCR during the follow-up period. The BCR-FS rate was significantly higher in patients with pT2+category tumors than in those with pT3a category tumors, and significantly lower in patients with pT2+category tumors than that in those with pT2 category tumors without PSM. The BCR-FS rate of patients with pT2+category tumors was significantly higher than that with pT3a category tumors with PSM but not significantly different from that with pT3a category tumors without PSM. In a multivariate analysis, the pathological T category considering pT2+category was one of independent predictive factors for BCR., Conclusions: This study support the hypothesis that the pT2+category disease is associated with a significantly increased risk of BCR in patients with organ-confined prostate cancer after RARP. As PSM can be avoided in some cases, urologists should continually seek to improve their operative skills and to reduce the rate of PSM, especially in patients with organ-confined prostate cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The estimated glomerular filtration rate is significantly decreased after nephroureterectomy. Deteriorating renal function likely affects the eligibility for cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. The present study was undertaken to identify preoperative factors for the prediction of postoperative renal function and develop a prediction model., Methods: Between June 1996 and January 2014, 110 patients who underwent radical nephroureterectomy at our institution were analyzed in this study. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. Univariate linear regression analyses were performed to investigate the correlation between postoperative estimated glomerular filtration rate and preoperative variables. A stepwise multivariate linear regression analysis was performed to identify independent predictors of postoperative estimated glomerular filtration rate., Results: Comparison of preoperative and postoperative estimated glomerular filtration rate for each patient showed a median difference of 13.1 ml/min/1.73 m(2). The postoperative estimated glomerular filtration rate was significantly lower than the preoperative estimated glomerular filtration rate (P < 0.001). On univariate analysis, age and preoperative estimated glomerular filtration rate were significantly correlated with postoperative estimated glomerular filtration rate. On multivariate analysis, age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictive factors of postoperative estimated glomerular filtration rate. The predicted postoperative estimated glomerular filtration rate, which was calculated using these independent factors, showed a significant correlation with the observed postoperative estimated glomerular filtration rate (correlation coefficient = 0.7533)., Conclusions: Age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictors of postoperative estimated glomerular filtration rate in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. The predicted postoperative estimated glomerular filtration rate based on these factors may be useful for choosing alternative management strategies such as neoadjuvant chemotherapy for patients with upper tract urothelial carcinoma., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Microcystins (MCs) are potent hepatotoxins produced by cyanobacteria in aquatic environments. MC-LR, a representative MC, strongly inhibits protein phosphatases 1 and 2A, leading to cell collapse in animal hepatocytes due to hyperphosphorylation of the cytoskeleton and apoptosis due to stimulation of the relevant systems. However, the molecular mechanisms and the metabolic pathways responsible for MC-LR toxicity are poorly understood. In the present study, we compared the cytotoxic effects of MC-LR in two cell lines: normal human hepatocytes (h-Nheps) and human hepatoma cell line HepG2. We also discussed the suitability of cellular assays for evaluating the toxicity of MCs. To obtain further insight into the molecular mechanism, the uptake, excretion, and intracellular distribution of MC-LR were analyzed using an antibody and assay kit targeting the catalytic subunit of protein phosphatase 2A (the PP2A assay kit). The responses toward MC-LR were distinctly different between the two cell lines. In HepG2 cells, MC-LR did not induce morphological change, did not reveal cytotoxicity, and accumulated to a lesser extent despite a slightly elevated expression of the MC transporter protein. MC-LR also did not alter the MC-binding potency of subcellular proteins. All these results indicate that HepG2 cells are inappropriate for the evaluation of MC-LR toxicity. The PP2A assay kits were useful not only for assessing PP2A-inhibitory potency, but also for determining the concentration of MCs in biological systems., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We present a case of a 67-year-old man with intussusception of the right ureter associated with a fibroepithelial polyp. The concentric sign and line sign are characteristic radiological findings in intussusception, and these findings could be seen in the present case. Although this entity is rare, its radiological findings are specific. Multidetector row computed tomography and its multiplanar reconstruction make the diagnosis feasible, although the qualitative diagnosis of the tumor was difficult., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To investigate the prognostic value of preoperative pyuria in patients with non-muscle-invasive bladder cancer., Methods: We retrospectively reviewed data from 237 patients diagnosed with non-muscle-invasive bladder cancer. Pyuria was defined as urine containing ≥5 white blood cells per high power field. The association between clinicopathological factors and recurrence was assessed by Cox univariate and multivariate analyses., Results: Preoperative pyuria was found in 116 (49.0%) patients. Pyuria was significantly associated with advanced age, positive cytology, multiple tumors, large tumor size, non-papillary tumors, T1 tumors and high-grade tumors. In univariate analysis of the entire patient population, pyuria, positive urine cytology, multiple tumors, pT1 tumors and no bacillus Calmette-Guérin were significantly associated with recurrence. Multivariate analysis showed that pyuria was an independent predictor of recurrence (hazard ratio 3.332, 95% confidence interval 2.052-5.410; P < 0.001), along with positive urine cytology, multiple tumors and no bacillus Calmette-Guérin therapy. Subanalysis of the patients who underwent bacillus Calmette-Guérin therapy also showed that pyuria was an independent predictor of recurrence (hazard ratio 2.062, 95% confidence interval 1.085-3.918, P = 0.027). The 2-year recurrence-free survival rate for patients with pyuria was significantly lower than for patients without pyuria (65.5% vs 80.7%; P = 0.027)., Conclusions: Preoperative pyuria seems to be significantly associated with recurrence in patients with non-muscle-invasive bladder cancer, and it might be a useful predictor for recurrence after bacillus Calmette-Guérin therapy., (© 2015 The Japanese Urological Association.)

Background: Switchgrass rust, caused by Puccinia emaculata, is an important disease of switchgrass, a potential biofuel crop in the United States. In severe cases, switchgrass rust has the potential to significantly affect biomass yield. In an effort to identify novel sources of resistance against switchgrass rust, we explored nonhost resistance against P. emaculata by characterizing its interactions with six monocot nonhost plant species. We also studied the genetic variations for resistance among Brachypodium inbred accessions and the involvement of various defense pathways in nonhost resistance of Brachypodium., Results: We characterized P. emaculata interactions with six monocot nonhost species and identified Brachypodium distachyon (Bd21) as a suitable nonhost model to study switchgrass rust. Interestingly, screening of Brachypodium accessions identified natural variations in resistance to switchgrass rust. Brachypodium inbred accessions Bd3-1 and Bd30-1 were identified as most and least resistant to switchgrass rust, respectively, when compared to tested accessions. Transcript profiling of defense-related genes indicated that the genes which were induced in Bd21after P. emaculata inoculation also had higher basal transcript abundance in Bd3-1 when compared to Bd30-1 and Bd21 indicating their potential involvement in nonhost resistance against switchgrass rust., Conclusion: In the present study, we identified Brachypodium as a suitable nonhost model to study switchgrass rust which exhibit type I nonhost resistance. Variations in resistance response were also observed among tested Brachypodium accessions. Brachypodium nonhost resistance against P. emaculata may involve various defense pathways as indicated by transcript profiling of defense related genes. Overall, this study provides a new avenue to utilize novel sources of nonhost resistance in Brachypodium against switchgrass rust.

Background: Recent studies have demonstrated associations between ABO blood groups and prognosis in various types of cancers. The aim of this study was to investigate the association between ABO blood groups and biochemical recurrence (BCR) after radical prostatectomy (RP)., Methods: A total of 555 patients with prostate cancer who underwent RP were included in the study. No patients received neoadjuvant and/or adjuvant therapy. The effect of ABO blood groups on BCR was examined using univariate and multivariate analyses., Results: During the follow-up period (mean, 52.0 months), 166 patients (29.9%) experienced BCR, with a 5-year BCR-free rate of 67.3%. Although the ABO blood group was not a significantly associated with BCR in the univariate analysis, it was an independent predictor of BCR in the multivariate analysis: blood type O patients had a significantly lower risk of BCR compared to type A patients (Hazard ratio, 0.608; 95% confidence interval, 0.410-0.902; P = 0.014). Further analyses revealed that surgical margin status confounded the assessment of the association between the ABO blood group and BCR. In the analyses of patients with a negative surgical margin, the 5-year BCR-free rate in blood type O patients was a significantly higher than that in type A patients (91.2% vs. 71.0%; P = 0.026)., Conclusion: Blood type O is significantly associated with a decreased risk of biochemical recurrence after radical prostatectomy. Further studies are needed to clarify the nature of this association.

Objectives: To examine biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients, and to develop a risk stratification model for biochemical recurrence., Methods: The study cohort consisted of 784 patients with localized prostate cancer who underwent robot-assisted radical prostatectomy without neoadjuvant or adjuvant endocrine therapy. The relationships of biochemical recurrence with perioperative findings were evaluated. The prognostic factors for biochemical recurrence-free survival were evaluated using Cox proportional hazard model analyses., Results: During the follow-up period, 80 patients showed biochemical recurrence. The biochemical recurrence-free survival rates at 1, 3, and 5 years were 92.2%, 85.2% and 80.1%, respectively. In univariate analysis, the prostate-specific antigen level, prostate-specific antigen density, biopsy Gleason score, percent positive core, pathological T stage, pathological Gleason score, lymphovascular invasion, perineural invasion and positive surgical margin were significantly associated with biochemical recurrence. In multivariate analysis, prostate-specific antigen density ≥0.4 (P = 0.0011), pathological T stage ≥3a (P = 0.002), pathological Gleason score ≥8 (P = 0.007) and positive surgical margin (P < 0.0001) were independent predictors of biochemical recurrence. The patients were stratified into three risk groups according to these factors. The 5-year biochemical recurrence-free survival rate was 89.4% in the low-risk group, 65.6% in the intermediate-risk group and 30.3% in the high-risk group., Conclusions: The prostate-specific antigen density, pathological T stage, pathological Gleason score and positive surgical margin were independent prognostic factors for biochemical recurrence. The risk stratification model developed using these four factors could help clinicians identify patients with a poor prognosis who might be good candidates for clinical trials of alternative management strategies., (© 2014 The Japanese Urological Association.)

Unlabelled: •, Premise of the Study: Plants will be an important component of advanced life support systems during space exploration missions. Therefore, understanding their biology in the spacecraft environment will be essential before they can be used for such systems.•, Methods: Seedlings of Arabidopsis thaliana were grown for 2 wk in the Biological Research in Canisters (BRIC) hardware on board the second to the last mission of the space shuttle Discovery (STS-131). Transcript profiles between ground controls and space-grown seedlings were compared using stringent selection criteria.•, Key Results: Expression of transcripts associated with oxidative stress and cell wall remodeling was repressed in microgravity. These downregulated genes were previously shown to be enriched in root hairs consistent with seedling phenotypes observed in space. Mutations in genes that were downregulated in microgravity, including two uncharacterized root hair-expressed class III peroxidase genes (PRX44 and PRX57), led to defective polar root hair growth on Earth. PRX44 and PRX57 mutants had ruptured root hairs, which is a typical phenotype of tip-growing cells with defective cell walls and those subjected to stress.•, Conclusions: Long-term exposure to microgravity negatively impacts tip growth by repressing expression of genes essential for normal root hair development. Whereas changes in peroxidase gene expression leading to reduced root hair growth in space are actin-independent, root hair development modulated by phosphoinositides could be dependent on the actin cytoskeleton. These results have profound implications for plant adaptation to microgravity given the importance of tip growing cells such as root hairs for efficient nutrient capture., (© 2015 Botanical Society of America, Inc.)

Microscopy is an important tool used for biological research and has played a crucial role toward understanding of cellular mechanisms and protein function. However, specific steps in processing of biological samples for microscopy warrant improvements to consistently generate data that can more reliably help in explaining mechanisms underlying complex biological phenomenon. Due to their small and fragile nature, some biological specimens such as Arabidopsis thaliana roots are vulnerable to damage during long sample preparation steps. Moreover, when specimens with a small diameter (typically less than 100 μm) are embedded in conventional silicone mold or capsule embedding, it is not only difficult to locate their orientation inside the capsule but also a challenge to obtain good median longitudinal sections. Specimen orientation in particular is crucial because understanding certain plant biological processes such as gravitropism rely on precisely knowing spatial information of cells and tissues of the plant organ being studied. Here we present a simple embedding technique to properly orient small plant organs so that the desired sectioning plane is achieved. This method is also inexpensive and can be accomplished with only minimal equipment and supplies.

Background: Nitroxoline is an FDA-approved antibiotic with potential antitumor activity. Here we evaluated whether nitroxoline has antiproliferative properties on glioma cell growth in vitro and in vivo using glioma cell lines and a genetically engineered PTEN/KRAS mouse glioma model., Methods: The effect of nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle arrest, invasion, and ability to induce an apoptotic cascade was determined in vitro. Magnetic resonance imaging was used to measure glioma volumes in genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy. Induction of apoptosis by nitroxoline was evaluated at the end of treatment using terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL)., Results: Nitroxoline inhibited the proliferation and invasion of glioblastoma cells in a time- and dose-dependent manner in vitro. Growth inhibition was associated with cell-cycle arrest in G1/G0 phase and induction of apoptosis via caspase 3 and cleaved poly(ADP-ribose) polymerase. In vivo, nitroxoline-treated mice had no increase in tumor volume after 14 days of treatment, whereas tumor volumes doubled in control mice. Histological examination revealed 15%-20% TUNEL-positive cells in nitroxoline-treated mice, compared with ∼5% in the control group., Conclusion: Nitroxoline induces apoptosis and inhibits glioma growth in vivo and in vitro. As an already FDA-approved treatment for urinary tract infections with a known safety profile, nitroxoline could move quickly into clinical trials pending confirmatory studies., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gender-based differences in disease onset in murine models of malignant peripheral nerve sheath tumor (MPNST) and in patients with Neurofibromatosis type-1-(NF-1)-associated or spontaneous MPNST has not been well studied., Methods: Forty-three mGFAP-Cre+;Ptenloxp/+;LSL-K-rasG12D/+ mice were observed for tumor development and evaluated for gender disparity in age of MPNST onset. Patient data from the prospectively collected UCLA sarcoma database (1974-2011, n = 113 MPNST patients) and 39 published studies on MPNST patients (n = 916) were analyzed for age of onset differences between sexes and between NF-1 and spontaneous MPNST patients., Results: Our murine model showed gender-based differences in MPNST onset, with males developing MPNST significantly earlier than females (142 vs. 162 days, p = 0.015). In the UCLA patient population, males also developed MPNST earlier than females (median age 35 vs. 39.5 years, p = 0.048). Patients with NF-1-associated MPNST had significantly earlier age of onset compared to spontaneous MPNST (median age 33 vs. 39 years, p = 0.007). However, expanded analysis of 916 published MPNST cases revealed no significant age difference in MPNST onset between males and females. Similar to the UCLA dataset, patients with NF-1 developed MPNST at a significantly younger age than spontaneous MPNST patients (p < 0.0001, median age 28 vs. 41 years) and this disparity was maintained across North American, European, and Asian populations., Conclusions: Although our preclinical model and single-institution patient cohort show gender dimorphism in MPNST onset, no significant gender disparity was detected in the larger MPNST patient meta-dataset. NF-1 patients develop MPNST 13 years earlier than patients with spontaneous MPNST, with little geographical variance.

Background: The risk factors of incisional surgical site infection (iSSI) after open radical cystectomy (ORC) have not been fully investigated. The aim of the present study is to examine factors correlated with iSSI development after ORC with intestinal urinary diversion., Methods: A total of 178 patients who had undergone ORC with intestinal urinary diversion between 2003 and 2012 at our institution were included in this retrospective study. Correlations between different perioperative factors and iSSI development were determined using univariate and multivariate logistic regression analyses., Results: iSSI was observed in 53 patients (29.8 %). In the univariate analysis, age, diabetes mellitus, thickness of subcutaneous fat (TSF), and allogeneic transfusion were significant predictors of iSSI development. Although subcutaneous closed-suction drainage (SCSD) was not a significant factor in univariate analysis, SCSD, age, and TSF were all finally identified as independent predictors of iSSI development (P = 0.020, P < 0.001, and P = 0.022, respectively). Further analyses demonstrated that SCSD was frequently used in patients with relatively thick subcutaneous fat tissue and that SCSD significantly decreased iSSI development in these patients., Conclusions: Advanced patient age, thick subcutaneous fat tissue, and the absence of SCSD were significantly associated with iSSI development in bladder cancer patients who underwent ORC with intestinal urinary diversion. SCSD may be a useful procedure for iSSI prevention, especially in patients with relatively thick subcutaneous fat tissue.

Objective: To identify predictive factors for multifocal lesions in patients with upper tract urothelial carcinoma (UTUC)., Patients and Methods: Between June 1996 and September 2013, a cohort of 147 patients underwent radical nephroureterectomy at our institution. Univariate and multivariate logistic regression analyses were performed to identify clinical covariates significantly associated with the multifocal UTUC lesions and establish a model to predict its occurrence., Results: In the univariate analyses, estimated glomerular filtration rate, hydronephrosis, history of bladder cancer, hemoglobin level, and Brinkman index were significantly associated with multifocal lesions. In the multivariate analysis, hydronephrosis (P = .010), history of bladder cancer (P = .017), Brinkman index >100 (P = .014), and hemoglobin level <11 g/dL (P = .031) were independent predictive factors for multifocal lesions. Using these independent factors, we calculated the predictive probability of multifocal lesions and predicted their occurrence. The predictive probability of multifocal lesions strongly correlated with their observed rate (regression coefficient = 0.9999)., Conclusion: An improved understanding of UTUC has led to various clinical guidelines being revised to recommend less invasive interventions in appropriate cases. Hydronephrosis, history of bladder cancer, Brinkman index, and hemoglobin level are independent predictive factors for multifocal lesions of UTUC. Although this study has limitations and additional studies are required to validate our findings, this information may aid in appropriate patient selection for partial ureterectomy and may be effectively incorporated into clinical practice., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Protein ubiquitination is a core regulatory determinant of neural development. Previous studies have indicated that the Nedd4-family E3 ubiquitin ligases Nedd4-1 and Nedd4-2 may ubiquitinate phosphatase and tensin homolog (PTEN) and thereby regulate axonal growth in neurons. Using conditional knockout mice, we show here that Nedd4-1 and Nedd4-2 are indeed required for axonal growth in murine central nervous system neurons. However, in contrast to previously published data, we demonstrate that PTEN is not a substrate of Nedd4-1 and Nedd4-2, and that aberrant PTEN ubiquitination is not involved in the impaired axon growth upon deletion of Nedd4-1 and Nedd4-2. Rather, PTEN limits Nedd4-1 protein levels by modulating the activity of mTORC1, a protein complex that controls protein synthesis and cell growth. Our data demonstrate that Nedd4-family E3 ligases promote axonal growth and branching in the developing mammalian brain, where PTEN is not a relevant substrate. Instead, PTEN controls neurite growth by regulating Nedd4-1 expression.

Elective Cesarean section performed before 39 weeks of gestation may be associated with increased risk of neonatal complications. We retrospectively investigated differences in the neonatal complication rate between 684 newborns delivered by elective Cesarean section at 37 weeks of gestation (n = 390) and those delivered by the same procedure at 38 weeks (n = 294) between 2006 and 2012 at our hospital in order to ascertain whether adverse outcomes differ between the groups. Newborns delivered at 37 weeks had a significantly higher incidence of neonatal intensive care unit admission (p = 0.03), adverse respiratory complications (p < 0.01), low birth weight (p < 0.001), and hypoglycemia (p < 0.005) than those delivered at 38 weeks. Compared with normal weight neonates, low birth weight neonates were more likely to have hypoglycemia (p < 0.001). Multivariate logistic regression analysis revealed that an adverse respiratory outcome was independently associated with gestational age (p < 0.01; odds ratio [OR], 3.26; 95% confidence interval [CI], 1.36-7.81), while hypoglycemia was independently associated with birth weight (p < 0.01; OR, 16.34; 95% CI, 7.72-34.56). Respiratory disorders were significantly associated with gestational age even in normal birth weight newborns without any other complications such as hyperbirilubinemia, hypoglycemia or bacterial infections. In conclusion, the incidence of neonatal complications was higher in newborns delivered at 37 weeks of gestation than in those delivered at 38 weeks via elective Cesarean section. Thus, the procedure should be scheduled at 38 weeks to improve neonatal outcomes.

Purpose: We investigated oncological outcomes in Japanese patients who underwent robot-assisted radical prostatectomy (RARP)., Materials and Methods: This study included 389 patients who underwent RARP at a single institution with a follow-up period of at least 1 year. Preoperative findings were compared with biochemical recurrence (BCR). Predictors of BCR-free survival (BCRFS) were evaluated by univariate and multivariate Cox proportional hazard model analyses, and a risk stratification model based on the relative risks of BCR was established., Results: Fifty incidences of BCR were noted during a median follow-up period of 28.7 months (range, 12.1-80.0 months). The BCRFS rate for the entire cohort at the median follow-up time was 85.9 %; the 1-, 3-, and 5-year estimates were 91.0, 85.1, and 81.1 %, respectively. From univariate analyses, prostate-specific antigen (PSA), PSA density, biopsy Gleason score, and percent positive core were significantly associated with BCR. Multivariate analysis showed that PSA [hazard ratio (HR), 2.75; p = 0.001], percent positive core (HR, 2.22; p = 0.001), and biopsy Gleason score (HR, 2.61; p = 0.007) were independent predictors of BCR., Conclusion: This study at a single Japanese center demonstrates that RARP provides a satisfactory BCRFS rate. This report provides a framework with which to estimate oncological outcomes in patients who underwent RARP for localized prostate cancer. Our results support the increased use of RARP for the treatment of localized prostate cancer in Japan.

The present study was undertaken to examine biochemical progression in patients who received salvage hormonal therapy (HT) for biochemical disease recurrence (BCR) after radical prostatectomy (RP), and to determine the optimal timing for the administration of HT. The study population consisted of 156 patients who underwent RP and received salvage HT for BCR. The starting point of this study was the timing of RP, and the endpoint was biochemical prostate-specific antigen (PSA) progression (castration-resistance) after HT. The mean follow-up period after surgery was 8.1 years. First, we excluded 18 patients with persistent PSA (≥ 0.2 ng/mL) after RP from an analysis below because their prognoses were significantly poorer compared with 138 patients whose PSA nadirs had reached <0.2 ng/mL. Multivariate analysis demonstrated that Gleason score ≥ 8 (p = 0.010, hazard ratio (HR) 3.02), and PSA doubling time (PSA-DT) <6 months (p = 0.001, HR 7.39) was independently associated with subsequent biochemical progression after HT. Using these two variables (Gleason score and PSA-DT), we could stratify patients into three risk groups for BCR after salvage HT. Regarding the optimal timing for HT administration for these high-risk patients with both risk factors (relative risk = 22.3), the PSA cutpoint of 1.0 ng/mL at the initiation of HT showed a significant difference in progression-free survival rates (p = 0.023). The findings indicated that for high-risk patients, salvage HT for BCR after PSA nadir (<0.2 ng/mL) should be started before the PSA level exceeds 1.0 ng/mL; otherwise, there is a significant risk of subsequent biochemical progression after HT.

Objective: To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy ina Japanese cohort., Methods: A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot., Results: With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate., Conclusions: The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

Purpose: To investigate the prognostic significance of infiltrative growth pattern (INF) and to develop a novel risk stratification model for disease-specific survival (DSS) in patients with upper urinary tract urothelial carcinoma (UTUC)., Methods: This study included 113 patients with UTUC treated with radical nephroureterectomy. Pathological features, including INF, were compared with DSS. INF was classified into 3 patterns (INFa, INFb, and INFc). The prognostic factors of DSS were evaluated with univariate and multivariate Cox proportional hazard model analyses. A risk stratification model based on the relative risks of DSS was then established., Result: Univariate analysis revealed that patients with high-grade tumor, pathological T stage ≥T3, a non-expanding infiltration pattern (INF ≥b), sessile-type carcinoma, the presence of lymphovascular invasion and positive lymph node involvement showed significantly lower survival rates than their respective counterparts. In the multivariate analysis, high grade tumor, positive lymph node involvement and INF ≥b were independent predictors for DSS (p < 0.05). The patients were stratified into 3 risk groups. The 5-year DSS rates were 94.4 % in the low-risk group, 67.5 % in the intermediate-risk group and 20.5 % in the high-risk group., Conclusion: In addition to lymph node involvement and pathological tumor grade, INF is a novel independent prognostic factor in patients with UTUC treated with radical nephroureterectomy. Our risk stratification model developed using these 3 factors may help clinicians identify patients with a poor prognosis who might be good candidates for clinical trials of innovative therapies.

Reduction of lignin levels in the forage legume alfalfa (Medicago sativa) by down-regulation of the monolignol biosynthetic enzyme hydroxycinnamoyl coenzyme A:shikimate hydroxycinnamoyl transferase (HCT) results in strongly increased digestibility and processing ability of lignocellulose. However, these modifications are often also associated with dwarfing and other changes in plant growth. Given the importance of nitrogen fixation for legume growth, we evaluated the impact of constitutively targeted lignin modification on the belowground organs (roots and nodules) of alfalfa plants. HCT down-regulated alfalfa plants exhibit a striking reduction in root growth accompanied by an unexpected increase in nodule numbers when grown in the greenhouse or in the field. This phenotype is associated with increased levels of gibberellins and certain flavonoid compounds in roots. Although HCT down-regulation reduced biomass yields in both the greenhouse and field experiments, the impact on the allocation of nitrogen to shoots or roots was minimal. It is unlikely, therefore, that the altered growth phenotype of reduced-lignin alfalfa is a direct result of changes in nodulation or nitrogen fixation efficiency. Furthermore, HCT down-regulation has no measurable effect on carbon allocation to roots in either greenhouse or 3-year field trials.

Background: Cytoreductive nephrectomy (CN) plays an important role in the multimodal treatment of metastatic renal cell carcinoma (RCC). However, certain patients experience rapid progression of the carcinoma following CN. This study aimed to investigate the value of neutrophil-to-lymphocyte ratio (NLR) in the selection of patients for CN., Methods: Records corresponding to 73 patients with metastatic RCC were retrospectively reviewed. Forty-eight patients underwent CN, and their overall survival (OS) and preoperative variables were analyzed. The OS of patients who did not undergo CN was used as a reference., Results: Univariate analysis showed that symptomatic tumors, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 1, hemoglobin level <12 g/dl, neutrophil count ≥ 5500/μL, C-reactive protein level ≥ 2.0 mg/dl, and NLR ≥ 4.0 were significantly associated with poor outcomes in patients who underwent cytoreductive nephrectomy. The median OS of patients with NLR ≥ 4.0 was 10.2 months, which was significantly shorter than that of patients with NLR <4.0 (36.5 months) (P = 0.0020). Multivariate analysis showed that NLR and ECOG-PS were independent predictors of OS in patients treated with CN. The OS of CN patients with NLR ≥ 4.0 and ECOG-PS ≥1 was similar to that of patients who did not undergo CN (8.4 vs. 6.1 months, P = 0.939)., Conclusions: Preoperative NLR elevation is significantly associated with poor outcomes in patients with metastatic RCC who underwent CN. Patients with NLR ≥4.0 and ECOG-PS ≥ 1 might not benefit from immediate CN after initial diagnosis.

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinical implication of preoperative serum total cholesterol (TC) level in patients with clear cell renal cell carcinoma (RCC)., Methods: The records of 364 patients with clear cell RCC who had undergone nephrectomy were retrospectively reviewed. The association among preoperative TC level, clinicopathologic factors, and oncological outcome in terms of cancer-specific survival (CSS) and recurrence-free survival period was analyzed by univariate and multivariate analyses., Results: As a continuous variable, lower serum TC level was found to be significantly associated with male sex, symptomatic tumor, advanced TNM stage, higher nuclear grade, microscopic venous invasion, poor Eastern Cooperative Oncology Group Performance Status, larger tumor size, elevated C-reactive protein level, and lower hemoglobin level. Univariate analysis showed that relatively lower preoperative serum TC level was associated with lower recurrence-free survival (P = .040) and CSS (P <.001) rates. Multivariate analysis indicated that in addition to pT stage, M stage, nuclear grade, and Eastern Cooperative Oncology Group Performance Status, serum TC level (hazard ratio, 0.988 per mg/dL; 95% confidence interval, 0.980-0.998; P = .019) was an independent predictor of CSS., Conclusion: Low preoperative serum TC level is associated with worse prognosis in patients with clear cell RCC. Consideration of preoperative serum TC level might thus provide additional prognostic information for patients with clear cell RCC., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to determine which of the following magnetic resonance (MR) imaging sequences is most effective for detecting prostate cancer: T2-weighted (T2W), dynamic contrast-enhanced (DCE) T1-weighted (T1W), or diffusion-weighted (DWI) imaging or apparent diffusion coefficient (ADC) mapping., Materials and Methods: We included 37 male patients with prostate cancer who underwent MR imaging before radical prostatectomy in this retrospective study. Sixty-four foci (>5 mm in size; 35 in the peripheral zone [PZ], 29 in the transitional zone [TZ]) were histopathologically determined to be prostate cancer. We determined the capacity of T2W, DCE-T1W, DWI, ADC mapping alone, and the combination of ADC mapping with DWI, and conventional MR sequences to detect prostate cancer, including their sensitivity and positive predictive value (PPV), with reference to the results obtained in histopathological examinations of whole-mount sections., Results: In the PZ, sensitivities were 31.4% (T2W), 37.1% (DCE-T1W), 51.4% (DWI), and 71.4% (ADC mapping); PPVs were 78.6% (T2W), 92.9% (DCE-T1W), 94.7% (DWI), and 96.0% (ADC mapping). Sensitivity was significantly higher of ADC mapping than other sequences. In the TZ, sensitivities were 55.1% (T2W), 44.8% (DCE-T1W), 82.8% (DWI), and 89.7% (ADC mapping); PPVs were 64.0% (T2W), 46.4% (DCE-T1W), 70.6% (DWI), and 72.2% (ADC mapping). Sensitivity was significantly higher of ADC mapping and DWI than conventional MR imaging, but there was no significant correlation between DWI/ADC mapping and T2W/DCE-T1W with respect to PPVs. Combining sequences did not improve sensitivity; only the PPV in the TZ improved when ADC mapping was combined with DCE-T1W., Conclusion: ADC mapping is the most effective standard MR imaging tool for detecting prostate cancer. The addition of DCE-T1W may improve the PPV of ADC mapping for diagnosing cancer in the TZ.

Leaf shape elaboration and organ separation are critical for plant morphogenesis. We characterized the developmental roles of lobed leaflet1 by analyzing a recessive mutant in the model legume Medicago truncatula. An ortholog of Arabidopsis thaliana argonaute7 (AGO7), Mt-AGO7/lobed leaflet1, is required for the biogenesis of a trans-acting short interfering RNA (ta-siRNA) to negatively regulate the expression of auxin response factors in M. truncatula. Loss of function in AGO7 results in pleiotropic phenotypes in different organs. The prominent phenotype of the ago7 mutant is lobed leaf margins and more widely spaced lateral organs, suggesting that the trans-acting siRNA3 (TAS3) pathway negatively regulates the formation of boundaries and the separation of lateral organs in M. truncatula. Genetic interaction analysis with the smooth leaf margin1 (slm1) mutant revealed that leaf margin formation is cooperatively regulated by the auxin/SLM1 (ortholog of Arabidopsis PIN-formed1) module, which influences the initiation of leaf margin teeth, and the TAS3 ta-siRNA pathway, which determines the degree of margin indentation. Further investigations showed that the TAS3 ta-siRNA pathway and no apical meristem (ortholog of Arabidopsis cup-shaped cotyledon) antagonistically regulate both leaf margin development and lateral organ separation, and the regulation is partially dependent on the auxin/SLM1 module.

Purpose: The aim of the present study was to investigate the learning curve and perioperative outcomes in 200 consecutive patients with prostate cancer who underwent robot-assisted radical prostatectomy (RARP)., Patients and Methods: Between August 2006 and August 2011, 200 patients with prostate cancer underwent RARP and were enrolled in this study. We prospectively collected the demographic data and analyzed the pathologic and functional outcomes. The operative outcomes analyzed were total operative time, estimated blood loss (EBL), positive surgical margin (PSM), incontinence, and perioperative complications. We also evaluated the relationship between the surgeon's experience and operative variables., Results: The sloping learning curve for this surgeon showed that total operative time was strongly correlated with the accumulation of experience for the initial 25 cases (|rs|=0.71, P<0.001). The average EBL was not strongly correlated with additional experience (|rs|<0.7). The PSM rate for the first 50 cases was significantly higher than that of the next 150 cases (34.8% vs 19.4%, P=0.035). The complication rate among the first 50 patients was significantly higher than that among the remaining 150 patients (32% vs 12.7%, P=0.002). The incontinence rate at 12 months was significantly higher for the first 100 cases compared with that for the next 100 cases (9.0% vs 1.0%, P=0.009). For the surgeon to optimize total operative time, PSM rate, complication rate, and incontinence rate, slope learning curves of 25, 50, 50, and 100 cases were needed., Conclusions: The functional and pathologic results of this minimally invasive procedure seemed to be promising. Distinct learning curves were observed with respect to operative time, PSM, complication rate, and incontinence rate. Exposure to 100 surgeries would be necessary for a surgeon to adequately master the required skills.

The evolution of lignin biosynthesis was critical in the transition of plants from an aquatic to an upright terrestrial lifestyle. Lignin is assembled by oxidative polymerization of two major monomers, coniferyl alcohol and sinapyl alcohol. Although two recently discovered laccases, LAC4 and LAC17, have been shown to play a role in lignin polymerization in Arabidopsis thaliana, disruption of both genes only leads to a relatively small change in lignin content and only under continuous illumination. Simultaneous disruption of LAC11 along with LAC4 and LAC17 causes severe plant growth arrest, narrower root diameter, indehiscent anthers, and vascular development arrest with lack of lignification. Genome-wide transcript analysis revealed that all the putative lignin peroxidase genes are expressed at normal levels or even higher in the laccase triple mutant, suggesting that lignin laccase activity is necessary and nonredundant with peroxidase activity for monolignol polymerization during plant vascular development. Interestingly, even though lignin deposition in roots is almost completely abolished in the lac11 lac4 lac17 triple mutant, the Casparian strip, which is lignified through the activity of peroxidase, is still functional. Phylogenetic analysis revealed that lignin laccase genes have no orthologs in lower plant species, suggesting that the monolignol laccase genes diverged after the evolution of seed plants.

Objective: Positive surgical margin after radical prostatectomy has been shown to be an independent predictive factor for biochemical and local recurrence in patients with prostate cancer. The present study was undertaken to identify predictive factors for positive surgical margin after robot-assisted radical prostatectomy in Japanese patients., Methods: Between August 2006 and September 2011, a cohort of 244 men underwent robot-assisted radical prostatectomy carried out by a single surgeon. Univariate and multivariate logistic regression analyses were carried out to identify clinical covariates significantly associated with an increased positive surgical margin. The preoperative variables included age, body mass index, prostate-specific antigen level, prostate-specific antigen density, clinical T stage, prostate volume, surgeon volume, number of positive cores and percentage of positive cores., Results: In the univariate analyses, serum prostate-specific antigen level, prostate-specific antigen density and surgeon volume were significantly associated with positive surgical margin. In the multivariate analysis, prostate-specific antigen density (hazard ratio 3.13, 95% confidence interval 1.57-6.24; P = 0.001) and surgeon volume (hazard ratio 2.15, 95% confidence interval 1.06-4.35; P = 0.034) were independent predictive factors for positive surgical margin. Using these two independent factors, we divided the patients into four groups and calculated the predictive probability of positive surgical margin. The predictive probability for positive surgical margin in each group was well correlated with the rates at 10.8% and 10.2%, 19.8% and 20.0%, 26.4% and 26.4%, an 43.5% and 43.3%, respectively., Conclusion: Prostate-specific antigen density and surgeon volume are independent predictors of positive surgical margin after robot-assisted radical prostatectomy. A combination of these two factors can provide useful information about positive surgical margins., (© 2013 The Japanese Urological Association.)

Transcription factors (TFs) are thought to regulate many aspects of nodule and symbiosis development in legumes, although few TFs have been characterized functionally. Here, we describe regulator of symbiosome differentiation (RSD) of Medicago truncatula, a member of the Cysteine-2/Histidine-2 (C2H2) family of plant TFs that is required for normal symbiosome differentiation during nodule development. RSD is expressed in a nodule-specific manner, with maximal transcript levels in the bacterial invasion zone. A tobacco (Nicotiana tabacum) retrotransposon (Tnt1) insertion rsd mutant produced nodules that were unable to fix nitrogen and that contained incompletely differentiated symbiosomes and bacteroids. RSD protein was localized to the nucleus, consistent with a role of the protein in transcriptional regulation. RSD acted as a transcriptional repressor in a heterologous yeast assay. Transcriptome analysis of an rsd mutant identified 11 genes as potential targets of RSD repression. RSD interacted physically with the promoter of one of these genes, VAMP721a, which encodes vesicle-associated membrane protein 721a. Thus, RSD may influence symbiosome development in part by repressing transcription of VAMP721a and modifying vesicle trafficking in nodule cells. This establishes RSD as a TF implicated directly in symbiosome and bacteroid differentiation and a transcriptional regulator of secretory pathway genes in plants.

Aim: Haemodynamically significant patent ductus arteriosus (hsPDA) is frequently observed in premature infants. This study was conducted to explore whether the blood BNP can be a valuable biomarker to assess the necessity of treatment for hsPDA in premature infants., Methods: Serial measurements of the blood BNP were performed during the first 5 days of life in premature infants with hsPDA (Group I) and those without hsPDA (Group N). The definition of the hsPDA was the PDA requiring treatment, such as indomethacin administration and/or surgical ligation., Results: Forty-six subjects were enrolled. Compared with Group N, Group I showed significantly higher level of blood BNP at postnatal 24-96 h and demonstrated the peak value at postnatal 24-48 h. With the ROC curve using the data at postnatal 24-48 h in Group I, we deduced the predictive value of 250 pg/mL of blood BNP for indomethacin treatment. Similarly, with the ROC curve using the maximal value of blood BNP within the first 5 days of life, the predictive value of 2000 pg/mL for surgical ligation was deduced., Conclusions: Blood BNP during early postnatal period can be a useful biomarker to assess the necessity of treatment for hsPDA in premature infants., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: Preoperative elevation of markers of systemic inflammation is associated with a poor outcome in several cancers. The purpose of this study was to evaluate the prognostic significance of preoperative systemic inflammatory markers in patients with non-metastatic upper urinary tract cancer (UUTC)., Methods: The records of 84 patients with non-metastatic UUTC who had undergone nephroureterectomy were reviewed, and the associations between preoperative clinical variables and recurrence-free survival (RFS) were analyzed by univariate and multivariate analyses., Results: Clinical tumor stage, neutrophil count, and neutrophil-to-lymphocyte ratio were significantly associated with RFS in univariate analysis. Multivariate analysis showed that clinical T stage (hazard ratio [HR], 3.009; 95 % confidence interval [CI], 1.149-9.321; p = 0.024) and neutrophil count (HR, 3.521; 95 % CI, 1.423-9.108; p = 0.007) were independent predictors of RFS. The 3-year RFS in patients with a neutrophil count <4,000/μL was significantly higher than that in patients with a neutrophil count ≥ 4,000/μL (82.9 vs. 51.0 %, p = 0.004). Based on clinical T stage (T2 or less vs. T3 or greater) and neutrophil count (<4,000 vs. ≥ 4,000/μL), patients were stratified into 3 groups: low, intermediate, and high risk groups. RFS rates were significantly different between the 3 groups (p = 0.0005)., Conclusions: Preoperative neutrophil count was an independent predictor of RFS in patients with non-metastatic UUTC. Stratification of patients based on neutrophil count and clinical T stage may be valuable for preoperative patient counseling and identifying patients with poor prognosis who may be candidates for neoadjuvant chemotherapy.

Symbiotic interaction between Medicago truncatula and Sinorhizobium meliloti results in the formation on the host roots of new organs, nodules, in which biological nitrogen fixation takes place. In infected cells, rhizobia enclosed in a plant-derived membrane, the symbiosome membrane, differentiate to nitrogen-fixing bacteroids. The symbiosome membrane serves as an interface for metabolite and signal exchanges between the host cells and endosymbionts. At some point during symbiosis, symbiosomes and symbiotic cells are disintegrated, resulting in nodule senescence. The regulatory mechanisms that underlie nodule senescence are not fully understood. Using a forward genetics approach, we have uncovered the early senescent nodule 1 (esn1) mutant from an M. truncatula fast neutron-induced mutant collection. Nodules on esn1 roots are spherically shaped, ineffective in nitrogen fixation, and senesce early. Atypical among fixation defective mutants isolated thus far, bacteroid differentiation and expression of nifH, Leghemoglobin, and DNF1 genes are not affected in esn1 nodules, supporting the idea that a process downstream of bacteroid differentiation and nitrogenase gene expression is affected in the esn1 mutant. Expression analysis shows that marker genes involved in senescence, macronutrient degradation, and remobilization are greatly upregulated during nodule development in the esn1 mutant, consistent with a role of ESN1 in nodule senescence and symbiotic nitrogen fixation.

Lignins are phenylpropanoid polymers, derived from monolignols, commonly found in terrestrial plant secondary cell walls. We recently reported evidence of an unanticipated catechyl lignin homopolymer (C lignin) derived solely from caffeyl alcohol in the seed coats of several monocot and dicot plants. We previously identified plant seeds that possessed either C lignin or traditional guaiacyl/syringyl (G/S) lignins, but not both. Here, we identified several dicot plants (Euphorbiaceae and Cleomaceae) that produce C lignin together with traditional G/S lignins in their seed coats. Solution-state NMR analyses, along with an in vitro lignin polymerization study, determined that there is, however, no copolymerization detectable (i.e., that the synthesis and polymerization of caffeyl alcohol and conventional monolignols in vivo is spatially and/or temporally separated). In particular, the deposition of G and C lignins in Cleome hassleriana seed coats is developmentally regulated during seed maturation; C lignin appears successively after G lignin within the same testa layers, concurrently with apparent loss of the functionality of O-methyltransferases, which are key enzymes for the conversion of C to G lignin precursors. This study exemplifies the flexible biosynthesis of different types of lignin polymers in plants dictated by substantial, but poorly understood, control of monomer supply by the cells.