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urothelium cancer

Takahiro Yoshida, Nikolai A Sopko, Max Kates, Xiaopu Liu, Gregory Joice, David J McConkey, Trinity J Bivalacqua
There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells...
February 16, 2018: Oncotarget
Satoshi Inoue, Hiroki Ide, Kazutoshi Fujita, Taichi Mizushima, Guiyang Jiang, Takashi Kawahara, Seiji Yamaguchi, Hiroaki Fushimi, Norio Nonomura, Hiroshi Miyamoto
Using preclinical models, we have recently found that ELK1, a transcriptional factor that activates downstream targets, including c-fos proto-oncogene, induces bladder cancer outgrowth. Here, we immunohistochemically determined the expression status of phospho-ELK1, an activated form of ELK1, in upper urinary tract urothelial carcinoma (UUTUC). Overall, phospho-ELK1 was positive in 47 (47.5%; 37 weak (1+) and 10 moderate (2+)) of 99 UUTUCs, which was significantly ( P = 0.002) higher than in benign urothelium (21 (25...
March 8, 2018: International Journal of Molecular Sciences
Liming Dong, Yanpei Li, Dongwei Xue, Yili Liu
The role of protein l-isoaspartate (d-aspartate) O-methyltransferase (PCMT1) in human cancer was generally cognized. The clinical significance and biological function of PCMT1 in bladder cancer is still unknown. PCMT1 mRNA and protein expression levels in bladder cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry, or western blot. The correlation between PCMT1 expression and clinicopathological factors was analyzed through immunohistochemistry in 108 bladder cancer patients. Loss-of-function and gain-of-function studies were conducted to explore the biological function of PCMT1 in bladder cancer cell lines in regulating cell proliferation, migration, and invasion...
March 8, 2018: IUBMB Life
C Wasén, M Ekstrand, M Levin, D Giglio
PURPOSE: Epidermal growth factor receptor (EGFr)-targeted therapy may be used in subgroups of patients with urinary bladder cancer. Here we assessed the role of EGFr in urothelial proliferation and migration in a two- and three-dimensional cell culture system. METHODS: UROtsa cells derived from normal urothelium and malignant T24 cells were cultured in a Type I collagen gel. Proliferation and migration of urothelial cells, in the absence and presence of the EGFr inhibitor cetuximab, were assessed with a proliferation test (ATCC) and with the Axioplan 2 imaging microscope with a motorized stage (Carl Zeiss), respectively...
March 5, 2018: International Urology and Nephrology
Raffaella Palumbo, Luca Licata, Federico Sottotetti, Barbara Tagliaferri, Emma Pozzi, Cristina Teragni, Erica Quaquarini, Antonio Bernardo
INTRODUCTION: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy. METHODS: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle...
2018: Oncology Research and Treatment
R Singh, A Mandhani, V Agrawal, Minal Garg
Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease...
January 18, 2018: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
Simon C Baker, Volker M Arlt, Radek Indra, Madeleine Joel, Marie Stiborova, Ian Eardley, Niaz Ahmad, Wolfgang Otto, Maximilian Burger, Peter Rubenwolf, David H Phillips, Jennifer Southgate
Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro...
January 11, 2018: Molecular Carcinogenesis
Prateek Kinra, S P Rashmi, Aftab Alam, Harkirat Singh, S C Dash
Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach...
October 2017: Indian Journal of Pathology & Microbiology
L Gao, P Yan, F F Guo, H J Liu, Z F Zhao
Recent studies have confirmed the existence of BDNF and tropomyosin-related kinase B (TrkB) in normal and cancerous urothelium. However, the corresponding mechanisms and upstream signal pathways of BDNF/TrkB have not been fully discovered. This study aimed to investigate the effects of miR-1-3p on bladder cancer (BC) by regulating BDNF-TrkB signal pathway. The expression of miR-1-3p and BDNF in BC tissues and cell lines were detected by Cancer Genome Atlas (TCGA) microarray analysis, RT-qPCR and western blot...
2018: Neoplasma
Yonghui Yu, Honglei Jin, Jiheng Xu, Jiayan Gu, Xin Li, Qipeng Xie, Haishan Huang, Jingxia Li, Zhongxian Tian, Guosong Jiang, Caiyi Chen, Feng He, Xue-Ru Wu, Chuanshu Huang
Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues...
December 18, 2017: International Journal of Cancer. Journal International du Cancer
Maximilian C Kriegmair, P Honeck, M Theuring, C Bolenz, M Ritter
PURPOSE: The aim of this pilot study was to assess the feasibility and value of wide-field autofluorescence imaging (AFI) for the detection of bladder cancer during transurethral resection of the bladder (TUR-B). METHODS: For imaging, the D-Light/AF System (Karl Storz GmbH, Tuttlingen, Germany) and a customized band pass filter (≈ 480-780 nm) at the eyepiece of the endoscope were used. The excitation light wavelength was 440 nm. Representative spectral measurements of tissue autofluorescence (AF) were performed using a spectrometer attached behind the AF band pass filter in selected patients...
December 6, 2017: World Journal of Urology
Christopher R Silvers, Hiroshi Miyamoto, Edward M Messing, George J Netto, Yi-Fen Lee
The mechanisms of bladder cancer progression are unknown, and new treatments and biomarkers are needed. Patient urinary extracellular vesicles (EVs) derive in part from bladder cancer cells and contain a specific protein cargo which may provide information about the disease. We conducted a proteomics study comparing EVs from the muscle-invasive bladder cancer (MIBC) cell line TCCSUP to EVs from normal urothelial line SVHUC. GO term analysis showed that TCCSUP EVs are enriched in proteins associated with the cell membrane, extracellular matrix, and inflammation and angiogenesis signaling pathways...
October 31, 2017: Oncotarget
Foteini D Tsikrika, Margaritis Avgeris, Panagiotis K Levis, Theodoros Tokas, Konstantinos Stravodimos, Andreas Scorilas
Clinical heterogeneity of bladder cancer prognosis requires the identification of bladder tumors' molecular profile to improve the prediction value of the established and clinically used markers. In this study, we have analyzed miR-221/222 cluster expression in bladder tumors and its clinical significance for patients' prognosis and disease outcome. The study included 387 tissue specimens. Following extraction, total RNA was polyadenylated at 3'-end and reversed transcribed. SYBR-Green based qPCR assays were performed for the quantification of miR-221/222 expression...
March 2018: Genes, Chromosomes & Cancer
Andrea Necchi, Gregory R Pond, Sumanta K Pal, Neeraj Agarwal, Daniel W Bowles, Elizabeth R Plimack, Evan Y Yu, Sylvain Ladoire, Jack Baniel, Simon Crabb, Gunter Niegisch, Sandy Srinivas, Dominik R Berthold, Jonathan E Rosenberg, Thomas Powles, Aristotelis Bamias, Lauren C Harshman, Joaquim Bellmunt, Matthew D Galsky
BACKGROUND: Patients with exclusive bone metastatic spread from urothelial carcinoma (UC) throughout their disease course represent a rare subgroup with unique clinical features. These patients deserved special consideration in a retrospective multicenter study. PATIENTS AND METHODS: Analyses were made from a pool of 1911 patients with a diagnosis of metastatic UC, from 23 centers. Baseline characteristics, access to treatment, and outcomes were analyzed according to metastatic spread...
November 1, 2017: Clinical Genitourinary Cancer
Angela M Halstead, Chiraag D Kapadia, Jennifer Bolzenius, Clarence E Chu, Andrew Schriefer, Lukas D Wartman, Gregory R Bowman, Vivek K Arora
RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of human bladder cancers. Here, we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers in human bladder cancer cells. Structure-function studies indicate that the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs...
November 16, 2017: ELife
A Bamias, K Tzannis, L C Harshman, S J Crabb, Y-N Wong, S Kumar Pal, U De Giorgi, S Ladoire, N Agarwal, E Y Yu, G Niegisch, A Necchi, C N Sternberg, S Srinivas, A Alva, U Vaishampayan, L Cerbone, M Liontos, J Rosenberg, T Powles, J Belmunt, M D Galsky
BackgroundCisplatin-based combination chemotherapy is the standard treatment for advanced urinary tract cancer (aUTC) but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival.Patients and MethodsThis was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology...
October 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Xuefeng Qiu, Kai Cao, Tingsheng Lin, Wei Chen, Ahu Yuan, Jinhui Wu, Yiqiao Hu, Hongqian Guo
Intravesical instillation of antitumor agents following transurethral resection of bladder tumors is the standard strategy for the treatment of superficial bladder cancers. However, the efficacy of current intravesical instillation is limited partly due to the poor permeability of the urothelium. We therefore aimed to develop a high-penetrating, target-releasing drug delivery system to improve the efficacy of intravesical instillation. PAMAM, a dendrimer, were conjugated with polyethylene glycol (PEG) to form PEG-PAMAM complex as a nanocarrier...
2017: International Journal of Nanomedicine
Anirudha Singh, Trinity J Bivalacqua, Nikolai Sopko
INTRODUCTION: In this review, we discuss major advancements and common challenges in constructing and regenerating a neo-urinary conduit (NUC). First, we focus on the need for regenerating the urothelium, the hallmark the urine barrier, unique to urinary tissues. Second, we focus on clinically feasible scaffolds based on decellularized matrices and molded collagen that are currently of great research interest. AIM: To discuss the major advancements in constructing a tissue-engineered NUC (TE-NUC) and the challenges involved in their successful clinical translation...
October 21, 2017: Sexual Medicine Reviews
Yuan-Chang Dai, Shou-Chieh Wang, Mohammad Mezbahul Haque, Wei-Han Lin, Lei-Chen Lin, Ching-Hsein Chen, Yi-Wen Liu
The bladder is an important organ for the storage of excreted water and metabolites. If metabolites with carcinogenic characteristics are present in urine, the urothelial lining of the bladder could be damaged and genetically altered. In this study, we analyzed the interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) on mouse bladder carcinogenesis. Our previous study found that arsenic affects BBN-altered urothelial enzymatic activity, protein expression, DNA oxidation and global DNA CpG methylation levels...
2017: PloS One
Shinjini Ganguly, Ayan Chandra, Dhruba J Chattopadhyay, Indu B Chatterjee
According to WHO classification system, non-invasive urothelial carcinoma represents urothelial carcinoma in situ (CIS) and dysplasia. Dysplastic urothelium often progresses to CIS that further advances to urothelial carcinoma (UC). The strongest risk factor for UC is cigarette smoking. However, the pathogenesis of cigarette smoke (CS)-induced UC is poorly understood. Earlier we had shown that p-benzoquinone (p-BQ), a major toxic quinone derived from p-benzosemiquinone of CS in vivo, is a causative factor for various CS-induced diseases...
2017: Toxicology Reports
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