No AccessJournal of UrologyInvestigative Urology1 Aug 2014Bladder Cancer Exosomes Contain EDIL-3/Del1 and Facilitate Progression Carla J. Beckham, Jayme Olsen, Peng-Nien Yin, Chia-Hao Wu, Huei-Ju Ting, Fred K. Hagen, Emelian Scosyrev, Edward M. Messing, Yi-Fen Lee BeckhamCarla Beckham Department Urology, University Rochester, New York , OlsenJayme Olsen Genetics, YinPeng-Nien Yin WuChia-Hao Wu TingHuei-Ju Ting Biological Science Technology, National Tainan, Taiwan, Republic China HagenFred...

Abstract Overproduction of reactive oxygen species (ROS), through either endogenous or exogenous sources, could induce DNA damage, and accumulation damage might lead to multistep carcinogenesis. The antioxidative effects vitamin D have been suggested by epidemiological many in vitro vivo laboratory studies. While exploring the prostate cells, we found that active form D, 1α, 25‐dihydroxyvitamin 3 (1,25‐VD), can protect nonmalignant human epithelial cell lines, BPH‐1 RWPE‐1, but not malignant...

It has been postulated that prostatic carcinogenesis is androgen dependent and androgens mediate their effects primarily through epithelial cells; however, definitive proof of hormone action in prostate cancer (PRCA) progression lacking. Here we demonstrate genetic loss function experiments PRCA dependency occurs via stromal receptors (AR) but not AR. Utilizing tissue recombination models carcinogenesis, AR was evaluated by surgical castration or deletion. Loss prevented malignant...

OBJECTIVE TR4 is a nuclear receptor without clear pathophysiological roles. We investigated the roles of hepatic in regulation lipogenesis and insulin sensitivity vivo vitro. RESEARCH DESIGN AND METHODS activity phosphorylation assays were carried out using hepatocytes various wild-type mutant constructs. Liver tissues from knockout, C57BL/6, db/db mice examined to investigate target gene stearoyl-CoA desaturase (SCD) 1 regulation. RESULTS transactivation inhibited via by metformin-induced...

The mechanisms of bladder cancer progression are unknown, and new treatments biomarkers needed. Patient urinary extracellular vesicles (EVs) derive in part from cells contain a specific protein cargo which may provide information about the disease. We conducted proteomics study comparing EVs muscle-invasive (MIBC) cell line TCCSUP to normal urothelial SVHUC. GO term analysis showed that enriched proteins associated with membrane, matrix, inflammation angiogenesis signaling pathways. Proteins...

The androgen receptor (AR) binds to response elements and regulates target genes via a mechanism involving coregulators. Here we demonstrate that the AR can interact with testicular orphan receptor-4 (TR4) function as repressor down-regulate TR4 by preventing binding its DNA. Interestingly, heterodimerization of also allows repress gene expression. Simultaneous exposure both receptors therefore could result in bidirectional suppression their genes. Together, these data coupling two different...

Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits.Intravitreal injections 35 microg/0.1 mL were administered to rabbits. Vitreous and aqueous humor levels determined at selected time intervals (1, 2, 4, 8, 16, 24, 48 hours), vitreous half-life was calculated. Four six eyes per point enucleated immediately stored -80 degrees C. Aqueous samples withdrawn before enucleation, obtained from ocular dissection isolation various intervals....

Regulation of phosphoenolpyruvate carboxykinase (PEPCK), the key gene in gluconeogenesis, is critical for glucose homeostasis response to quick nutritional depletion and/or hormonal alteration.Here, we identified testicular orphan nuclear receptor 4 (TR4) as a PEPCK regulator modulating via transcriptional mechanism. TR4 transactivates 490-bp promoter-containing luciferase reporter activity by direct binding responsive element (TR4RE) located at -451 -439 promoter region. Binding TR4RE was...

// Sayeda Yasmin-Karim 1 , Michael R. King 2 Edward M. Messing Yi-Fen Lee Departments of Urology and Pathology Laboratory Medicine, Chemical Engineering, University Rochester, NY 14642 Department Biomedical Cornell University, Ithaca, 14853 Correspondence to: Lee, e-mail: YiFen_Lee@URMC.Rochester.edu Keywords: prostate cancer, circulatory tumor cell, cancer cell rolling adhesion, E-selectin ligand-1, Received: July 31, 2014      Accepted: September 16, Published:...

Markers of stromal activation at future metastatic sites may have prognostic value and allow clinicians to identify abolish the pre-metastatic niche prevent metastasis. In this study, we evaluate tenascin-C as a marker formation in bladder cancer patient lymph nodes.Tenascin-C expression benign nodes was compared between (n = 20) non-metastatic 27) patients with muscle-invasive cancer. Urinary extracellular vesicle (EV) cytokine levels were measured an antibody array examine potential...

Amino acid sequence analysis indicates that the human TR4 orphan receptor (TR4) is a member of estrogen/thyroid subfamily steroid/thyroid superfamily and recognizes AGGTCA direct repeat (DR) hormone response element. Here we demonstrate using electrophoretic mobility shift assay binds specifically to DR with spacing 1 5 base pairs (DR1 DR5), which are elements for retinoic (RAR) retinoid X (RXR), respectively. A reporter gene chloramphenicol acetyltransferase demonstrated repressed...

Early studies suggest that TR4 nuclear receptor is a key transcriptional factor regulating various biological activities, including reproduction, cerebella development, and metabolism. Here we report mice lacking ( −/− ) exhibited increasing genome instability defective oxidative stress defense, which are associated with premature aging phenotypes. At the cellular level, observed rapid growth arrest less resistance to DNA damage in mouse embryonic fibroblasts (MEFs) vitro. Restoring or...

While the TR4 orphan receptor (TR4) is able to repress expression of its target genes via interaction with direct repeat 1-hormone response element (DR1-HRE) and DR2-HRE, we now report that can also induce transcriptional activity reporter gene containing a DR4-HRE chloramphenicol acetyltransferase assay. Electrophoretic mobility shift assay Scatchard analysis reveal strong binding affinity (dissociation constant=2 nm) between DR4-HRE. The induction mediated by was detected not only in...

The key expression of the simian virus 40 (SV40) major late promoter could be repressed by human TR4 orphan receptor via +55 region SV40 (nucleotide numbers 368-389, 5′-GTTAAGGTTCGTAGGTCATGGA-3′). Using coupled in vitro transcribed and translated with a molecular mass 67.3 kilodaltons, electrophoretic mobility shift assay showed specific binding dissociation constant 1.09 nM between oligonucleotides. In addition, chloramphenicol acetyltransferase demonstrated that this can function as...

Prostate cancer is initially responsive to hormonal therapy, but cancers inevitably progress in an androgen-independent fashion with virtually all tumors evolving into more aggressive androgen refractory disease. Immunohistological comparisons of cyclooxygenase 2 (COX-2) expressions 3 pairs prostate patients before and after the combined blockade (CAB) therapy show elevated COX-2 expressions. This observation from clinical specimens further supported by vitro laboratory data using human...

// Jong-Wei Hsu 1,2 , Peng-Nien Yin 1 Ronald Wood 3 James Messing 4 Edward and Yi-Fen Lee Department of Urology, University Rochester, New York, USA 2 Pathology, Obstetrics Gynecology, Cornell University, Ithaca, York Correspondence: Lee, email: Keywords : vitamin D, Bacillus Calmette-Guérin, bladder cancer, immunotherapy, interleukin 8 Received October 14, 2013 Accepted November 17, Published 19, Abstract Calmette-Guérin (BCG), a vaccine against tuberculosis(TB), has been used proven to be...

Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration—neoadjuvant or adjuvant—remains unclear. To determine efficacy combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial neoadjuvant anti-PD-1 (αPD-1) anti-CTLA-4 (αCTLA-4), combination cisplatin-gemcitabine, for patients cancer prior to radical cystectomy. In addition, novel murine model spontaneous was...

In situ hybridization analysis demonstrated that abundant testicular orphan receptor (TR4) transcripts were detected in kidney, intestine, and bone, which are vitamin D3 target organs. Cell transfection studies also the expression of gene, 25-hydroxyvitamin 24-hydroxylase, can be repressed by TR4 through high affinity binding (Kd = 1.32 nM) to direct repeat 3 response element (DR3VDRE). This TR4-mediated repression DR3VDRE is contrast our earlier report could induce thyroid hormone genes...