Background: Tumor vascularity is a potential predictor of treatment outcomes in metastatic renal cell carcinoma (mRCC), and contrast enhancement of tumors in computed tomography (CT) is correlated significantly with microvessel density. In this study, the authors investigated whether tumor enhancement in contrast-enhanced CT (CECT) is useful for predicting outcomes in patients with mRCC who are receiving antiangiogenic therapy.
Methods: Attenuation values were reviewed retrospectively on CECT images of all metastatic lesions in 66 patients from February 2007 to November 2008.
Pathways regulating threonine, methionine and isoleucine metabolism are very efficiently interconnected in plants. As both threonine and methionine serve as substrates for isoleucine synthesis, their synthesis and catabolism under different developmental and environmental conditions also influence isoleucine availability. Together, methionine gamma-lyase and threonine deaminase maintain the isoleucine equilibrium in plants under varied substrate availabilities.
View Article and Find Full Text PDFBackground: Gene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the expression of their target genes in specific biological processes. Despite their importance, regulators involved in diverse biological processes still remain largely unrevealed.
View Article and Find Full Text PDFObjective: To determine whether the presence of prostate stem cell antigen (PSCA) mRNA in peripheral blood can predict biochemical recurrence (BCR) after radical prostatectomy in patients with high-risk prostate cancer.
Methods: High-risk disease was defined based on the presence of any one of the following three risk factors: prostate-specific antigen (PSA) > or = 20 ng/ml, a biopsy Gleason score (GS) > or = 8, or clinical stage > or = T2c. Nested reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect PSCA mRNA-bearing cells in peripheral blood.
Zebrafish mutants have traditionally been obtained by using random mutagenesis or retroviral insertions, methods that cannot be targeted to a specific gene and require laborious gene mapping and sequencing. Recently, we and others have shown that customized zinc-finger nucleases (ZFNs) can introduce targeted frame-shift mutations with high efficiency, thereby enabling directed creation of zebrafish gene mutations. Here we describe a detailed protocol for constructing ZFN expression vectors, for generating and introducing ZFN-encoding RNAs into zebrafish embryos and for identifying ZFN-generated mutations in targeted genomic sites.
View Article and Find Full Text PDFPurpose: We evaluated the clinical significance of lymphovascular invasion in transurethral resection of bladder tumor specimens in patients with newly diagnosed T1 urothelial carcinoma of the bladder.
Materials And Methods: Enrolled in the study were 118 patients with newly diagnosed T1 urothelial carcinoma of the bladder who underwent transurethral resection of bladder tumor between 2001 and 2007. Patient records were retrieved from a prospectively maintained bladder cancer database.
The information and resources generated from diverse "omics" technologies provide opportunities for producing novel biological knowledge. It is essential to integrate various kinds of biological information and large-scale omics data sets through systematic analysis in order to describe and understand complex biological phenomena. For this purpose, we have developed a Web-based system, Plant MetGenMAP, which can comprehensively integrate and analyze large-scale gene expression and metabolite profile data sets along with diverse biological information.
View Article and Find Full Text PDFEngineered zinc-finger nucleases (ZFNs) form the basis of a broadly applicable method for targeted, efficient modification of eukaryotic genomes. In recent work, we described OPEN (oligomerized pool engineering), an 'open-source,' combinatorial selection-based method for engineering zinc-finger arrays that function well as ZFNs. We have also shown in direct comparisons that the OPEN method has a higher success rate than previously described 'modular-assembly' methods for engineering ZFNs.
View Article and Find Full Text PDFWe report here homologous recombination (HR)-mediated gene targeting of two different genes in human iPS cells (hiPSCs) and human ES cells (hESCs). HR-mediated correction of a chromosomally integrated mutant GFP reporter gene reaches efficiencies of 0.14%-0.
View Article and Find Full Text PDFAn efficient method for making directed DNA sequence modifications to plant genes (gene targeting) is at present lacking, thereby frustrating efforts to dissect plant gene function and engineer crop plants that better meet the world's burgeoning need for food, fibre and fuel. Zinc-finger nucleases (ZFNs)-enzymes engineered to create DNA double-strand breaks at specific loci-are potent stimulators of gene targeting; for example, they can be used to precisely modify engineered reporter genes in plants. Here we demonstrate high-frequency ZFN-stimulated gene targeting at endogenous plant genes, namely the tobacco acetolactate synthase genes (ALS SuRA and SuRB), for which specific mutations are known to confer resistance to imidazolinone and sulphonylurea herbicides.
View Article and Find Full Text PDFBackground: MicroRNAs (miRNAs) are small and noncoding RNAs that play important roles in various biological processes. They regulate target mRNAs post-transcriptionally through complementary base pairing. Since the changes of miRNAs affect the expression of target genes, the expression levels of target genes in specific biological processes could be different from those of non-target genes.
View Article and Find Full Text PDFBackground: Customized zinc finger nucleases (ZFNs) form the basis of a broadly applicable tool for highly efficient genome modification. ZFNs are artificial restriction endonucleases consisting of a non-specific nuclease domain fused to a zinc finger array which can be engineered to recognize specific DNA sequences of interest. Recent proof-of-principle experiments have shown that targeted knockout mutations can be efficiently generated in endogenous zebrafish genes via non-homologous end-joining-mediated repair of ZFN-induced DNA double-stranded breaks.
View Article and Find Full Text PDFA lab-scale anaerobic filter process was operated for the treatment of purified terephthalic acid (PTA) wastewater, and the influences of organic loading disturbances on the process performance were investigated. After about 15 month operation, the COD removal efficiency was maintained at 79% under the volumetric loading rate of 5.05 kg-COD/m3/d and the hydraulic retention time (HRT) of 50 h.
View Article and Find Full Text PDFZinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this 'modular assembly' approach do not always function well in vivo.
View Article and Find Full Text PDFMotivation: MicroRNAs miRNAs play important roles in gene regulation and are regarded as key components in gene regulatory pathways. Systematically understanding functional roles of miRNAs is essential to define core transcriptional units regulating key biological processes. Here, we propose a method based on the probabilistic graphical model to identify the regulatory modules of miRNAs and the core regulatory motifs involved in their ability to regulate gene expression.
View Article and Find Full Text PDFBackground And Purpose: We evaluated the results of a second transurethral resection (TUR) performed in patients referred after an initial TUR for nonmuscle invasive bladder cancer.
Patients And Methods: From April 2001 to January 2008, patients who were referred for a second opinion and who underwent a second TUR at our institution were included in this study. Patients who had noninvasive bladder cancer and received the second TUR less than 8 weeks after the initial TUR were included in this analysis.
Purpose: This study was undertaken to investigate the outcomes associated with docetaxel treatment of Korean patients with hormone-refractory prostate cancer (HRPC) and to compare its clinical efficacies in 1st and 2nd-line settings.
Patients And Methods: This study was retrospectively performed and included 47 patients with HRPC. The 1st-line group consisted of 19 patients who had not undergone prior chemotherapy, and the 2nd-line group consisted of 28 patients who underwent prior chemotherapy.
Objective: To identify markers that predict the synchronous or metachronous development of bladder cancer in patients with upper urinary tract (UUT) tumors.
Materials And Methods: Between March 2001 and December 2005, we identified 38 consecutive patients who had been histologically diagnosed as having transitional cell carcinoma in the renal pelvis and ureter. These patients were divided into 2 groups (n = 19 per group): group 1 patients with metachronous or synchronous bladder cancer, and group 2 patients with UUT tumors only.
Zinc fingers are the most abundant DNA-binding motifs encoded by eukaryotic genomes and one of the best understood DNA-recognition domains. Each zinc finger typically binds a 3-nt target sequence, and it is possible to engineer zinc-finger arrays (ZFAs) that recognize extended DNA sequences by linking together individual zinc fingers. Engineered zinc-finger proteins have proven to be valuable tools for gene regulation and genome modification because they target specific sites in a genome.
View Article and Find Full Text PDFThe authors designed this study to determine the clinical effectiveness of trimodality treatment, i.e., transurethral resection of a bladder tumor (TURBT) and concurrent chemoradiotherapy (CRT).
View Article and Find Full Text PDFCustom-made zinc-finger nucleases (ZFNs) can induce targeted genome modifications with high efficiency in cell types including Drosophila, C. elegans, plants, and humans. A bottleneck in the application of ZFN technology has been the generation of highly specific engineered zinc-finger arrays.
View Article and Find Full Text PDFMethods of modifying the human genome precisely and efficiently hold great promise for revolutionizing the gene therapy arena. One particularly promising technology is based on the homologous recombination (HR) pathway and is known as gene targeting. Until recently, the low frequency of HR in mammalian cells, and the resulting dependence on selection to identify these rare events, has prevented gene targeting from being applied in a therapeutic context.
View Article and Find Full Text PDFObjective: Of the many surgical options available for ureteral reconstruction during surgery for non-urologic pelvic malignancies, the efficacy of transureteroureterostomy (TUU) was investigated.
Methods: Ureteral reconstruction was dichotomized as follows: group 1, end-to-end ureteroureterostomy and ureteroneocystostomy (UNC) with or without a psoas hitch; and group 2, TUU. TUU was preferably performed when partial bladder invasion was suspected or patients had undergone prior surgery or radiotherapy.
Introduction: Frequent mutations or deletions of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are reported in bladder cancer, while there are few studies which evaluated PTEN as a clinical prognostic parameter of superficial bladder cancer. We prospectively evaluated PTEN expression in patients with superficial bladder cancer by immunohistochemical staining and defined the value of PTEN mutations in predicting tumor behavior of superficial bladder cancer.
Materials And Methods: A total of 190 patients were enrolled in this study.