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urothelium cancer

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https://www.readbyqxmd.com/read/28163793/uromark-a-urinary-biomarker-assay-for-the-detection-of-bladder-cancer
#1
Andrew Feber, Pawan Dhami, Liqin Dong, Patricia de Winter, Wei Shen Tan, Mónica Martínez-Fernández, Dirk S Paul, Antony Hynes-Allen, Sheida Rezaee, Pratik Gurung, Simon Rodney, Ahmed Mehmood, Felipe Villacampa, Federico de la Rosa, Charles Jameson, Kar Keung Cheng, Maurice P Zeegers, Richard T Bryan, Nicholas D James, Jesus M Paramio, Alex Freeman, Stephan Beck, John D Kelly
BACKGROUND: Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149932/aquaporin-3-expression-loss-in-urothelial-carcinoma-association-with-tumor-invasion-depth-but-not-with-grading
#2
Johannes Breyer, Wolfgang Otto, Maximilian Burger, Arndt Hartmann, Peter C Rubenwolf
We have previously provided molecular evidence of expression of aquaporin 3 (AQP3) in normal human urothelium and in UBC of various stages. Whereas former studies demonstrated that loss of AQP3 was associated with invasive and high-grade disease and worse progression-free and cancer-specific survival, this report investigates the expression of AQP3 in associated CIS. Contrary to what we had expected, all CIS specimens were shown to exhibit strong AQP3 expression, suggesting loss of AQP3 in UBC is primarily associated with the ability of tumor cells for invasion but not with grading as sign of dedifferentiation...
January 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28109014/urothelial-generation-and-regeneration-in-development-injury-and-cancer
#3
REVIEW
Caihong Wang, Whitney Trotter Ross, Indira U Mysorekar
Homeostatic maintenance and repair of the urothelium upon injury are required for a functional bladder in both healthy and disease conditions. Understanding the cellular and molecular mechanisms underlying the urothelial regenerative response is key to designing strategies for tissue repair and ultimately treatments for urologic diseases including urinary tract infections, voiding dysfunction, painful bladder syndrome and bladder cancer. In this article, we review studies on urothelial ontogeny during development and regeneration following various injury modalities...
January 20, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28101348/evans-blue-mediated-white-light-detection-of-non-muscle-invasive-bladder-cancer-a-preclinical-feasibility-and-safety-study-using-a-rat-bladder-urothelial-cell-carcinoma-model
#4
Sanne Elsen, Evelyne Lerut, Frank Van Der Aa, Ben Van Cleynenbreugel, Hendrik Van Poppel, Peter De Witte
Photodynamic diagnosis (PDD) improves the detection of non-muscle-invasive bladder cancer (NMIBC). However, white-light (WL) cystoscopy remains the technique routinely used in urological clinics. A more cost-effective but equally performant alternative to PDD may encompass the use of an intense tumoritropic dye in combination with WL cystoscopy. Using a preclinical setting, we investigated the practical aspects of the use of Evans blue (EB) dye for the possible future detection of NMIBC using WL cystoscopy...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28081549/microrna-promoter-methylation-a-new-tool-for-accurate-detection-of-urothelial-carcinoma
#5
Nuno André Padrão, Sara Monteiro-Reis, Jorge Torres-Ferreira, Luís Antunes, Luís Leça, Diana Montezuma, João Ramalho-Carvalho, Paula C Dias, Paula Monteiro, Jorge Oliveira, Rui Henrique, Carmen Jerónimo
BACKGROUND: Urothelial carcinoma (UC) is the most common cancer affecting the urinary system, worldwide. Lack of accurate early detection tools entails delayed diagnosis, precluding more efficient and timely treatment. In a previous study, we found that miR-129-2 and miR-663a were differentially methylated in UC compared with other genitourinary tract malignancies. Here, we evaluated the diagnostic performance of those microRNAs in urine. METHODS: Promoter methylation levels of miR-129-2 and miR-663a were assessed, using real-time quantitative methylation-specific PCR, in UC tissue samples (using normal urothelium as control) and, subsequently, in urine samples from UC and other genitourinary malignancies...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28074261/perioperative-chemotherapy-in-upper-tract-urothelial-carcinoma-a-comprehensive-review
#6
REVIEW
Atiqullah Aziz, Jakub Dobruch, Kees Hendricksen, Luis A Kluth, Andrea Necchi, Aidan Noon, Michael Rink, Florian Roghmann, Roland Seiler, Paolo Gontero, Wassim Kassouf, Shahrokh F Shariat, Evanguelos Xylinas
PURPOSE: To evaluate the role of neoadjuvant (NAC) and adjuvant chemotherapy (AC) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: A comprehensive review of the current literature was performed searching for all studies investigating NAC and AC in UTUC in MEDLINE and https://clinicaltrials.gov , prior to April 2016. The following keywords were used: "ureteral neoplasms," "urothelium," "ureter," "upper tract urothelial," "chemotherapy," "adjuvant," "neoadjuvant" and relevant variants...
January 10, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/27960233/iatrogenic-changes-in-the-urinary-tract
#7
REVIEW
Antonio Lopez-Beltran, Gladell P Paner, Rodolfo Montironi, Maria R Raspollini, Liang Cheng
A handful of therapeutic procedures are used to treat malignancies of the urinary tract, most frequently intravesical immunotherapy or chemotherapy, but also neoadjuvant systemic chemotherapy. These treatment modalities produce morphological changes in the urothelium that can be mistaken for carcinoma; in particular, these therapies frequently mimic urothelial carcinoma in situ (CIS) urothelial dysplasia or true invasive neoplasia. Drugs such as mitomycin C used after transurethral resection of bladder tumour to reduce recurrences, bacillus Calmette-Guérin (BCG) intravesical immunotherapy to treat high-risk non-muscle-invasive bladder cancer and urothelial CIS and platin-based systemic chemotherapy to improve postcystectomy disease-specific survival are examples of therapy-related atypia seen in the urinary tract...
January 2017: Histopathology
https://www.readbyqxmd.com/read/27932416/a-phase-ii-trial-of-dovitinib-in-bcg-unresponsive-urothelial-carcinoma-with-fgfr3-mutations-or-over-expression-hoosier-cancer-research-network-trial-hcrn-12-157
#8
Noah M Hahn, Trinity J Bivalacqua, Ashley E Ross, George J Netto, Alexander S Baras, Jong Chul Park, Carolyn Chapman, Timothy A Masterson, Michael O Koch, Richard Bihrle, Richard S Foster, Thomas A Gardner, Liang Cheng, David R Jones, Kyle McElyea, George E Sandusky, Timothy Breen, Ziyue Liu, Costantine Albany, Marietta L Moore, Rhoda A Loman, Angela Reed, Scott A Turner, Francine B de Abreu, Torrey L Gallagher, Gregory J Tsongalis, Elizabeth R Plimack, Richard E Greenberg, Daniel M Geynisman
PURPOSE: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment resistant, molecularly enriched NMIUC population. EXPERIMENTAL DESIGN: A multi-site pilot phase 2 trial was conducted. Key eligibility criteria included: BCG unresponsive NMIUC (> 2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913307/urothelium-adherent-ion-triggered-liposome-in-gel-system-as-a-platform-for-intravesical-drug-delivery
#9
Shruti GuhaSarkar, Prachi More, Rinti Banerjee
Instillations of therapeutic agents into the urinary bladder have limited efficacy due to drug washout and inadequate attachment to and penetration into the bladder wall. Instilled nanoparticles alone have low stability and high susceptibility to washout, while gel-based systems are difficult to administer and retain. To overcome disadvantages of current technologies, a biodegradable, in situ-gelling liposome-in-gel (LP-Gel) system was developed for instillation into the bladder, composed of nano-sized, fluidizing liposomes incorporated into a "smart" biopolymeric, urine-triggered hydrogel...
January 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27898096/on-a-fox-hunt-functions-of-fox-transcriptional-regulators-in-bladder-cancer
#10
REVIEW
Hironobu Yamashita, Vasty Osei Amponsa, Joshua I Warrick, Zongyu Zheng, Peter E Clark, Jay D Raman, Xue-Ru Wu, Cathy Mendelsohn, David J DeGraff
Genomic and transcriptional studies have identified discrete molecular subtypes of bladder cancer. These observations could be the starting point to identify new treatments. Several members of the forkhead box (FOX) superfamily of transcription factors have been found to be differentially expressed in the different bladder cancer subtypes. In addition, the FOXA protein family are key regulators of embryonic bladder development and patterning. Both experimental and clinical data support a role for FOXA1 and FOXA2 in urothelial carcinoma...
November 29, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27777073/mtorc2-activation-is-regulated-by-the-urokinase-receptor-upar-in-bladder-cancer
#11
Andrew M Hau, Mariah Z Leivo, Andrew S Gilder, Jing-Jing Hu, Steven L Gonias, Donna E Hansel
Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27729990/uroplakins-and-their-potential-applications-in-urology
#12
REVIEW
Michal Andrzej Matuszewski, Krzysztof Tupikowski, Łukasz Dołowy, Beata Szymańska, Janusz Dembowski, Romuald Zdrojowy
INTRODUCTION: Urothelium is a highly specialized type of epithelium covering the interior of the urinary tract. One of the structures responsible for its unique features are urothelial plaques formed from glycoprotein heteropolymers, the uroplakins. Four types of uroplakins are known - UPIa, UPIb, UPII, UPIII. Herein we review the current status of knowledge about uroplakins and discuss their potential clinical applications. MATERIAL AND METHODS: A PubMed search was conducted to find original and review papers about uroplakins...
2016: Central European Journal of Urology
https://www.readbyqxmd.com/read/27726966/nomogram-based-prediction-of-overall-survival-in-patients-with-metastatic-urothelial-carcinoma-receiving-first-line-platinum-based-chemotherapy-retrospective-international-study-of-invasive-advanced-cancer-of-the-urothelium-risc
#13
Andrea Necchi, Guru Sonpavde, Salvatore Lo Vullo, Daniele Giardiello, Aristotelis Bamias, Simon J Crabb, Lauren C Harshman, Joaquim Bellmunt, Ugo De Giorgi, Cora N Sternberg, Linda Cerbone, Sylvain Ladoire, Yu-Ning Wong, Evan Y Yu, Simon Chowdhury, Gunter Niegisch, Sandy Srinivas, Ulka N Vaishampayan, Sumanta K Pal, Neeraj Agarwal, Ajjai Alva, Jack Baniel, Ali-Reza Golshayan, Rafael Morales-Barrera, Daniel W Bowles, Matthew I Milowsky, Christine Theodore, Dominik R Berthold, Gedske Daugaard, Srikala S Sridhar, Thomas Powles, Jonathan E Rosenberg, Matthew D Galsky, Luigi Mariani
BACKGROUND: The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of cisplatin-treated patients. OBJECTIVE: To develop a new model based on real-world patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient-level data from 29 centers were collected, including metastatic UC and first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011...
February 2017: European Urology
https://www.readbyqxmd.com/read/27720671/genotoxic-and-cytotoxic-effects-of-the-environmental-pollutant-3-nitrobenzanthrone-on-bladder-cancer-cells
#14
Galina Reshetnikova, Viktoriya S Sidorenko, Terry Whyard, Mark Lukin, Wayne Waltzer, Takeji Takamura-Enye, Victor Romanov
3-Nitrobenzanthrone (3-NBA), a potential human carcinogen, is present in diesel exhaust. The main metabolite of 3-NBA, 3-aminobenzanthrone, was detected in urine of miners occupationally exposed to diesel emissions. Environmental and occupational factors play an important role in development of bladder cancer (BC), one of the most frequent malignancies. It is expected that exposure of urothelium to 3-NBA and its metabolites may induce BC initiation and/or progression. To test this hypothesis, we studied geno- and cytotoxicity of 3-NBA using an in vitro BC model...
October 5, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27720534/systematic-review-on-the-fate-of-the-remnant-urothelium-after-radical-cystectomy
#15
Georgios Gakis, Peter C Black, Bernard H Bochner, Stephen A Boorjian, Arnulf Stenzl, George N Thalmann, Wassim Kassouf
CONTEXT: Urothelial carcinoma is considered a pan-urothelial disease. As such, the remnant urothelium in the upper urinary tract and urethra following radical cystectomy (RC) remains at risk for secondary urothelial tumors (SUTs). OBJECTIVE: To describe the incidence, diagnosis, treatment, and outcomes of patients with SUTs after RC. EVIDENCE ACQUISITION: A systematic search was conducted using PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2016 reporting on malignant diseases of the urothelium after RC for bladder cancer...
October 6, 2016: European Urology
https://www.readbyqxmd.com/read/27716887/intravesical-electro-osmotic-administration-of-mitomycin-c
#16
Savino M Di Stasi, Cristian Verri, Francesco Celestino, Francesco De Carlo, Vincenzo Pagliarulo
Bladder cancer is very common and most cases are diagnosed as nonmuscle invasive disease, which is characterized by its propensity to recur and progress. Intravesical therapy is used to delay recurrence and progression, while cystectomy is reserved for patients who are refractory to transurethral resection and intravesical therapy. There is an increasing interest in methods to enhance the delivery of intravesical chemotherapeutic agents to improve efficacy. In vitro and in vivo studies demonstrated that electro-osmosis of mitomycin C (MMC) is more effective in delivering this drug into the urothelium, lamina propria, and superficial muscle layers of the bladder wall than is passive transport...
October 4, 2016: Urologia
https://www.readbyqxmd.com/read/27713144/rgs6-is-an-essential-tumor-suppressor-that-prevents-bladder-carcinogenesis-by-promoting-p53-activation-and-dnmt1-downregulation
#17
Jianqi Yang, Lance T Platt, Biswanath Maity, Katelin E Ahlers, Zili Luo, Zhibo Lin, Bandana Chakravarti, Stella-Rita Ibeawuchi, Ryan W Askeland, Jolanta Bondaruk, Bogdan A Czerniak, Rory A Fisher
Urinary bladder cancer (UBC) is largely caused by exposure to toxic chemicals including those in cigarette smoke (i.e. BBN). An activating SNP in RGS6 is associated with a pronounced reduction in UBC risk, especially among smokers. However, the mechanism underlying this reduction remains unknown. Here we demonstrate that RGS6 is robustly expressed in human urothelium, where urothelial cell carcinoma originates, and is downregulated in human UBC. Utilizing RGS6-/- mice we interrogated a possible role for RGS6 as a tumor suppressor using the BBN-induced bladder carcinogenesis model that closely recapitulates human disease...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27696932/improving-diagnostic-molecular-tests-to-monitor-urothelial-carcinoma-recurrence
#18
Laura-Maria Krabbe, Solomon L Woldu, Shahrokh F Shariat, Yair Lotan
The high recurrence rates associated with non-muscle invasive bladder cancer require close surveillance with cystoscopy, an invasive and expensive procedure with risk of missing cancer. Finding an accurate urinary biomarker that can detect recurrent disease would represent a significant advancement in management. Areas covered: This review summarizes the commercially-available urinary biomarkers including cytology, UroVysion, BTA, NMP22, uCyt+, and Cxbladder assays. Additionally, we review recent investigational urinary biomarkers that hold promise in bladder cancer surveillance...
November 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27690298/glucuronidation-and-ugt-isozymes-in-bladder-new-targets-for-the-treatment-of-uroepithelial-carcinomas
#19
REVIEW
Vikram L Sundararaghavan, Puneet Sindhwani, Terry D Hinds
Bladder cancer has been linked to numerous toxins which can be concentrated in the bladder after being absorbed into the blood and filtered by the kidneys. Excessive carcinogenic load to the bladder urothelium may result in the development of cancer. However, enzymes within the bladder can metabolize carcinogens into substrates that are safer. Importantly, these proteins, namely the UGT's (uridine 5'-diphospho-glucuronosyltransferases), have been shown to possibly prevent bladder cancer. Also, studies have shown that the UGT1 expression is decreased in uroepithelial carcinomas, which may allow for the accumulation of carcinogens in the bladder...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27688767/targeted-imaging-of-urothelium-carcinoma-in-human-bladders-by-an-icg-phlip-peptide-ex-vivo
#20
Jovana Golijanin, Ali Amin, Anna Moshnikova, Joseph M Brito, Timothy Y Tran, Ramona-Cosmina Adochite, Gregory O Andreev, Troy Crawford, Donald M Engelman, Oleg A Andreev, Yana K Reshetnyak, Dragan Golijanin
Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
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