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Urothelial cell carcinoma

Karl Patterson, Lovleen Arya, Sarah Bottomley, Susan Morgan, Angela Cox, James Catto, Helen E Bryant
RECQ helicases are a family of enzymes with both over lapping and unique functions. Functional autosomal recessive loss of three members of the family BLM, WRN and RECQL4, results in hereditary human syndromes characterized by cancer predisposition and premature aging, but despite the finding that RECQL5 deficient mice are cancer prone, no such link has been made to human RECQL5. Here we demonstrate that human urothelial carcinoma of the bladder (UCC) has increased expression of RECQL5 compared to normal bladder tissue and that increasing RECQL5 expression can drive proliferation of normal bladder cells and is associated with poor prognosis...
October 15, 2016: Oncotarget
Daniel J Zaccarini, Xiaobing Deng, Jamie Tull, Charlene Maciak, Alfredo L Valente, Shengle Zhang
The characteristic immunoprofile for the diagnosis of synovial sarcoma, a neoplasm of unclear tissue origin, is expression of transducer-like enhancer of split 1 (TLE-1), CD99, partial expression of cytokeratin, and epithelial membrane antigen by immunohistochemistry (IHC). Diagnostic dilemma or misdiagnosis can occur due to overlap in IHC and morphology with carcinomas, and particularly poorly differentiated and metastatic tumors. The frequency of TLE-1 and CD99 expression in carcinomas by IHC has not been previously assessed...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Philip H Abbosh, Jonathan E Rosenberg, Elizabeth R Plimack
There are very few biomarkers used to diagnose bladder cancer and no clinically approved biomarkers for prediction or prognostication of this disease. All currently available biomarkers are based on urine tests, and thus, they may not be applicable to patients with extravesical tumors. Biopsy of metastatic sites requires an invasive procedure, whereas serum-based markers, which can be easily obtained and serially measured, thus have obvious merit. These deficiencies may be overcome with advances in genome sequencing, identification of circulating tumor cells, and RNA-, protein-, and DNA-based biomarkers...
October 14, 2016: Urologic Oncology
Bishoy M Faltas, Davide Prandi, Scott T Tagawa, Ana M Molina, David M Nanus, Cora Sternberg, Jonathan Rosenberg, Juan Miguel Mosquera, Brian Robinson, Olivier Elemento, Andrea Sboner, Himisha Beltran, Francesca Demichelis, Mark A Rubin
Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated urothelial carcinoma is characterized by intra-patient mutational heterogeneity, and the majority of mutations are not shared; (ii) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (iii) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways; and (iv) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime...
October 17, 2016: Nature Genetics
Juan Xing, Somak Roy, Sara E Monaco, Liron Pantanowitz
BACKGROUND: Urinary diversion specimens from patients who undergo radical cystectomy are often submitted for urine cytology to screen for recurrent urothelial carcinoma. The objective of the current study was to investigate the frequency and cytohistologic features of cancer recurrence in diversion urine specimens. METHODS: A 10-year retrospective review of archival urinary diversion specimens was conducted. For abnormal cytology cases, cytology slides were reviewed, and their cytomorphology and available corresponding histopathology were documented...
October 14, 2016: Cancer
Łukasz Piotr Fus, Barbara Górnicka
INTRODUCTION: Bladder cancer is the most common urinary tract malignancy in western countries. In recent years, extensive research has suggested that angiogenesis plays an important role in bladder cancer biology, contributing to tumor growth and progression. MATERIAL AND METHODS: In this review, we discuss general mechanisms of angiogenesis and highlight the influence of pro- and anti-angiogenic factors, and cancer stem cells on bladder cancer biology, their relation to disease progression, and potential use in novel targeted therapies...
2016: Central European Journal of Urology
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...
October 7, 2016: European Urology
Chi-Cheng Chen, Chi-Ping Huang, Teng-Fu Hsieh, Wei-Kai Chiu, Wen-Ling Chang, Chih-Rong Shyr
Interactions between infiltrating macrophages in the tumor microenvironment (TME) and tumor cells contribute to tumor progression. The potential impacts of recruited macrophages to the upper urinary tract urothelial cell carcinomas (UUTUCs) progression remain unclear. Here we found human UUTUCs might recruit more macrophages than surrounding normal urothelial cells in human clinical specimens and in in vitro co-culture experiments with UUTUC cells and macrophages. The consequences of recruiting more macrophages to UUTUCs might then enhance UUTUC cell growth, migration and invasion...
2016: American Journal of Cancer Research
Di Sun, Cong Wei, Yi Li, Qijie Lu, Wei Zhang, Bing Hu
Totally 85 patients with 93 renal lesions who underwent contrast-enhanced ultrasound (CEUS) were retrospectively studied with quantitative analysis to evaluate its value in the differential diagnosis of renal tumor histotypes. CEUS characteristics were analysed including the enhancement patterns, peak intensity, homogeneity of enhancement, and pseudocapsule. Quantitative parameters of peak intensity (P) and time to peak (TP) were measured with QontraXt software, and the index "relative enhancement percentage" ΔP% and "difference in TP between tumor and cortex" ΔTP were used to quantify the CEUS features of renal tumors...
October 11, 2016: Scientific Reports
H Mochizuki, M Breen
Recent discovery of the BRAF V595E mutation in a variety of canine cancers indicates that mutant BRAF may represent a novel therapeutic target. Presence of RAS mutations is associated with poor tumour response to BRAF inhibition but has not been investigated in BRAF-mutated canine cancers. The aim of this study was to evaluate the mutational status of three RAS genes (HRAS, KRAS and NRAS) in four types of canine carcinoma with and without the BRAF V595E mutation. Novel HRAS mutations were identified in 18% (3/17) of oral squamous cell carcinoma, whereas 17% (3/18) of pulmonary carcinoma carried KRAS or NRAS mutations...
October 6, 2016: Veterinary and Comparative Oncology
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
Hiroaki Matsumoto, Masaru Munemori, Kosuke Shimizu, Nakanori Fujii, Keita Kobayashi, Ryo Inoue, Yoshiaki Yamamoto, Kazuhiro Nagao, Hideyasu Matsuyama
OBJECTIVES: To investigate the expression levels of E-cadherin, Snail, Twist and Bmi-1 in the human upper tract urothelial carcinoma, and to assess whether these factors could be prognostic markers. METHODS: Immunohistochemistry was carried out to determine the expression of E-cadherin, Snail, Twist and Bmi-1 in upper tract urothelial carcinoma samples from 144 patients that underwent total nephroureterectomy between January 1995 and December 2010. The patient population had a median age of 71 years, and comprised 104 men and 40 women, with a median follow-up period of 40 months...
October 5, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Anurag Sharma, Shivani Sharma, Niharika Patnaik, Dinesh Pradhan, Kaliprasad Satapathy, Manas R Pradhan, Sambit K Mohanty
BACKGROUND: The incidence of primary small cell carcinoma (SCC) of the urinary bladder is extremely rare. We sought to analyze the cytologic and immunophenotypic features of SCC of the urinary bladder in urine and reassert the importance of cytologic examination of urine specimens for diagnosis of this tumor. METHODS: We studied the clinical and cytomorphologic features in the presurgical urine specimens (4 voided urine and 2 bladder-washing specimens) of histopathologically and immunohistochemically proven cases of SCC of the urinary bladder...
October 4, 2016: Acta Cytologica
Jong-Joo Lee, Mikyoung Kim, Hyoung-Pyo Kim
Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion...
September 29, 2016: BMB Reports
Qun Fang, XiaoYan Chen, XuTing Zhi
BACKGROUND In this study, we aimed to investigate the association between UCA1 and miR-27b in gastric cancer and further study their involvement in multi-drug resistance (MDR) of gastric cancer. MATERIAL AND METHODS The microarray data of dysregulated lncRNAs in gastric cancer tissues was retrieved in the GEO dataset. QRT-PCR analysis was performed to assess UCA1 expression based on 28 paired cancerous and peritumoral normal tissues. The human gastric cancer cell line SGC-7901, and SGC-7901 derived Adriamycin (doxorubicin) resistant SGC-7901/ADR, cisplatin resistant SGC-7901/DDP, and 5-FU resistant SGC-7901/FU cells were used as in vitro cell models to assess the effect of UCA1 and miR-27b on MDR...
October 1, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
M-O Grimm
Immune checkpoint inhibitors are establishing itselves as a new systemic treatment option (in addition to chemotherapy and targeted therapy) for metastatic tumours. (Re)activating the immune system, these antibodies may lead to impressive remissions lasting for a long time in some patients. Regarding urological tumours, the anti-PD-1 antibody Nivolumab (Opdivo(®)) has been approved this year for advanced, previously treated renal cell carcinoma. In the United States, Atezolizumab (Tecentriq(®)) has been approved for metastatic urothelial carcinoma after platinum-based chemotherapy...
September 2016: Aktuelle Urologie
Armin Soave, Sabine Riethdorf, Roland Dahlem, Gunhild von Amsberg, Sarah Minner, Lars Weisbach, Oliver Engel, Margit Fisch, Klaus Pantel, Michael Rink
To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch(®) system. Platinum-based AC was administered in 50 patients (27...
September 26, 2016: International Journal of Cancer. Journal International du Cancer
Changjie Jiao, Zhiming Song, Jianming Chen, Jing Zhong, Weibin Cai, Suke Tian, Songlin Chen, Yunfeng Yi, Yun Xiao
Esophageal cancer (EC) is one of the most common gastrointestinal cancers, which leads to the sixth ranking of cancer-related death. Long non-coding RNAs (lncRNAs) play pivotal roles in many biological processes. lncRNA human urothelial carcinoma associated 1 (UCA1) is significantly upregulated and functions as an important oncogene in many types of human cancers. However, the role of UCA1 in EC and its underlying mechanism remains unclear. In the present study, we demonstrated that UCA1 was significantly upregulated in EC tissues and associated with poor prognosis...
September 22, 2016: Oncology Reports
Vignesh Shanmugam, Brian Geraghty, Robert DeSimone, Rana S Hoda
INTRODUCTION: Urothelial carcinoma (UCC) of the bladder is the most common malignancy of the urinary tract. The performance of urine cytology (UCy) after radical cystectomy (RC) and urinary diversion is quite variable and there is no consensus regarding its role in post-treatment surveillance. The goal of this study is to retrospectively review the diagnostic value of positive (suspicious or positive for malignancy) diverted urine cytology (DUCy) in the detection of urinary tract recurrence of UCC...
September 26, 2016: Diagnostic Cytopathology
Giulia I Lane, Tracy M Downs, Ayman Soubra, Amrita Rao, Lauren Hemsley, Christopher Laylan, Fangfang Shi, Badrinath Konety
PURPOSE: Hexaminolevulinate hydrochloride (HAL) with blue light cystoscopy (BLC) is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy (WLC) for the detection of urothelial cell carcinoma. In this study we examine the tolerability of the repeat use of WLC+BLC. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent WLC+BLC with HAL during a 34-month period at two institutions. We compared the incidence of adverse events (AEs) after initial and subsequent procedures...
September 21, 2016: Journal of Urology
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