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bladder cancer sequence

Wei Tse Li, Hao Zheng, Vincent Nguyen, Jessica Wang-Rodriguez, Weg M Ongkeko
Though bladder urothelial carcinoma is the most common form of bladder cancer, advances in its diagnosis and treatment have been modest in the past few decades. To evaluate miRNAs as putative disease markers for bladder urothelial carcinoma, this study develops a process to identify dysregulated miRNAs in cancer patients and potentially stratify patients based on the association of their microRNAome phenotype to genomic alterations. Using RNA sequencing data for 409 patients from the Cancer Genome Atlas, we examined miRNA differential expression between cancer and normal tissues and associated differentially expressed miRNAs with patient survival and clinical variables...
March 12, 2018: Neoplasia: An International Journal for Oncology Research
Sho Sugawara, Yasutaka Yamada, Takayuki Arai, Atsushi Okato, Tetsuya Idichi, Mayuko Kato, Keiichi Koshizuka, Tomohiko Ichikawa, Naohiko Seki
Analyses of microRNA (miRNA) expression signatures obtained by RNA sequencing revealed that some passenger miRNAs (miR-144-5p, miR-145-3p, miR-149-3p, miR-150-3p, and miR-199a-3p) acted as anti-tumor miRNAs in several types of cancer cells. The involvement of passenger strands in the pathogenesis of human cancer is a novel concept. Based on the miRNA signature of bladder cancer (BC) obtained by RNA sequencing, we focused on both strands of the miR-223-duplex (miR-223-5p and miR-223-3p) and investigated their functional significance in BC cells...
March 14, 2018: Journal of Human Genetics
Lara Kujtan, Arif Hussain, Janakiraman Subramanian, Ashiq Masood
PURPOSE OF REVIEW: Recent advances in next-generation sequencing have allowed for detailed molecular analysis of urothelial carcinomas, with potentially significant clinical implications for personalized treatment. Our objective in this review is to highlight studies from the past year that have furthered the understanding of urothelial cancer genomics. RECENT FINDINGS: Recent studies by The Cancer Genome Atlas consortium further characterized urothelial carcinomas via molecular subtyping, and a schema was proposed to match each subtype with potential therapeutic implications...
March 13, 2018: Current Opinion in Oncology
Peiye Shen, Ying Jing, Ruiyun Zhang, Mei-Chun Cai, Pengfei Ma, Haige Chen, Guanglei Zhuang
Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin...
March 14, 2018: Oncogene
Takayuki Arai, Miki Fuse, Yusuke Goto, Kanya Kaga, Akira Kurozumi, Yasutaka Yamada, Sho Sugawara, Atsushi Okato, Tomohiko Ichikawa, Tomonori Yamanishi, Naohiko Seki
Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic inflammatory disease that affects the bladder. The symptoms of IC vary, including feeling an urgent need for immediate urination and of needing to urinate often, as well as bladder or pelvic pain. Despite its high incidence, no molecular diagnostic methods are available for IC, and the molecular pathogenesis is unknown. microRNAs (miRNA) can regulate expression of RNA transcripts in cells and aberrant expression of miRNAs is associated with several human diseases...
March 12, 2018: Journal of Human Genetics
David K Lau, Rebecca Y Tay, Yvonne H Yeung, Fiona Chionh, Jennifer Mooi, Carmel Murone, Effie Skrinos, Timothy J Price, John M Mariadason, Niall C Tebbutt
BACKGROUND: Advanced biliary tract cancers (BTCs) have a poor prognosis and limited treatment options. This exploratory phase II study aimed to evaluate the activity of the mTOR inhibitor everolimus in advanced BTC and explore prognostic biomarkers. METHODS: Patients with advanced BTCs, who had not received chemotherapy for advanced disease, were enroled to receive everolimus (10 mg daily). The primary endpoint was disease control rate (DCR) at 12 weeks. Secondary endpoints included overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events...
March 12, 2018: British Journal of Cancer
Ralf Kittler, Christine Shiang, Ryan Hutchinson, Rahul K Kollipara, Payal Kapur, Francis Franto, Yair Lotan
Purpose: Low-grade (LG) urothelial carcinomas of the bladder (UCB) are common malignancies that are costly to surveil and rarely progress to life threatening, high-grade (HG) malignancies. It is unknown if the progression of LG to HG is a result of second primary tumors or transformation of existing LG tumors. We examined tumor genetics in patients with grade progression in urothelial carcinoma and compared to patients with no progression. Results: Five patients were identified with progression...
February 6, 2018: Oncotarget
Haibiao Xie, Hengji Zhan, Qunjun Gao, Jianfa Li, Qun Zhou, Zhicong Chen, Yuhan Liu, Mengting Ding, Huizhong Xiao, Yuchen Liu, Weiren Huang, Zhiming Cai
Both oncogenic transcription factors (TFs) and microRNAs (miRNAs) play important roles in human cancers, acting as transcriptional and post-transcriptional regulators, respectively. These phenomena raise questions about the ability of an artificial device to simultaneously regulate miRNAs and TFs. In this study, we aimed to construct artificial long non-coding RNAs, "alncRNAs", and to investigate their therapeutic effects on bladder cancer cell lines. Based on engineering principles of synthetic biology, we combined tandem arrayed aptamer cDNA sequences for TFs with tandem arrayed cDNA copies of binding sites for the miRNAs to construct alncRNAs...
March 1, 2018: Cancer Letters
Myung-Shin Lee, Jisu Lee, Suhyuk Lee, Seung-Min Yoo, Joo Heon Kim, Won Tae Kim, Wun-Jae Kim, Jinsung Park
Heat shock protein 27 (HSP27) is highly expressed in many cancers, and its prognostic and predictive value has been reported. HSP27 knockdown using siRNA or OGX-427 (an anti-sense oligonucleotide sequence targeting HSP27) is reported to have anti-cancer effects and to enhance chemosensitivity of cancer cells to chemotherapeutic agents. However, conflicting results have been reported regarding the clinical significance of HSP27 in bladder cancer (BC). Furthermore, long-term suppression of HSP27 has not been investigated in BC...
January 30, 2018: Oncotarget
Filip Roudnicky, Sun Young Yoon, Susanna Poghosyan, Simon Schwager, Cedric Poyet, Giorgia Vella, Samia B Bachmann, Sinem Karaman, Jay W Shin, Vivianne I Otto, Michael Detmar
Thrombospondin-2 (TSP2) is an anti-angiogenic matricellular protein that inhibits tumor growth and angiogenesis. Tumor-associated blood vascular endothelial cells (BECs) were isolated from human invasive bladder cancers and from matched normal bladder tissue by immuno-laser capture microdissection. Exon expression profiling analyses revealed a particularly high expression of a short TSP2 transcript containing only the last 9 (3') exons of the full-length TSP2 transcript. Using 5' and 3' RACE (rapid amplification of cDNA ends) and Sanger sequencing, we confirmed the existence of the shorter transcript of TSP2 (sTSP2) and determined its sequence which completely lacked the anti-angiogenic thrombospondin type 1 repeats domain...
February 22, 2018: Oncogene
Alexander P Glaser, Damiano Fantini, Yiduo Wang, Yanni Yu, Kalen J Rimar, Joseph R Podojil, Stephen D Miller, Joshua J Meeks
APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. We explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival using sequencing data from The Cancer Genome Atlas (n = 395), Beijing Genomics Institute (n = 99), and Cancer Cell Line Encyclopedia. Tumors were split into "APOBEC-high" and "APOBEC-low" based on APOBEC enrichment. Patients with APOBEC-high tumors have better overall survival compared to those with APOBEC-low tumors (38...
January 12, 2018: Oncotarget
Shuzo Tamura, Yin Wang, Brendan Veeneman, Daniel Hovelson, Armand Bankhead, Luke J Broses, Guadalupe Lorenzatti Hiles, Monica Liebert, John R Rubin, Kathleen C Day, Maha Hussain, Nouri Neamati, Scott Tomlins, Philip L Palmbos, Petros Grivas, Mark L Day
Background: The HER family of proteins (EGFR, HER2, HER3 and HER4) have long been thought to be therapeutic targets for bladder cancer, but previous clinical trials targeting these proteins have been disappointing. Second generation agents may be more effective. Objective: The aim of this study was to evaluate responses to two second-generation irreversible tyrosine kinase inhibitors, dacomitinib and afatinib, in bladder cancer cell lines. Methods: Cell lines were characterized by targeted next generation DNA sequencing, RNA sequencing, western blotting and flow cytometry...
January 20, 2018: Bladder Cancer
Ilaria J Russo, Yongwon Ju, Naheema S Gordon, Maurice P Zeegers, K K Cheng, Nicholas D James, Richard T Bryan, Douglas G Ward
Background: TERT promotor mutations are present in >75% of bladder tumours; these mutations are also detectable in urine. Previous studies have used urinary pellet DNA, and semi-quantitative methods unsuitable for detecting very low mutant allele frequencies. Objective: In this proof-of-principle study we use ddPCR to count the DNA molecules with wt and mutant TERT sequences in urinary cfDNA from patients whose bladder cancers harbour TERT mutations. Methods: Urinary cfDNA prepared from the urine from 104 bladder cancer patients was analysed...
January 20, 2018: Bladder Cancer
Hongyi Li, Lin Liu, Qinglei Shi, Alto Stemmer, Hong Zeng, Yi Li, Mengchao Zhang
To compare the detection of bladder neoplasms and image quality among the diffusion-weighted imaging (DWI) acquired by the prototype single-shot echo-planar-imaging (ss-EPI) sequence for integrated slice-specific dynamic shimming (iShim), readout segmentation of long variable echo trains (RESOLVE) and conventional ss-EPI sequences.Around 63 patients with 77 bladder lesions were enrolled. The MR protocol included T1WI, T2WI and 3 types of DWI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each DWI for the detection of bladder tumor were computed...
December 2017: Medicine (Baltimore)
Emil Christensen, Iver Nordentoft, Søren Vang, Karin Birkenkamp-Demtröder, Jørgen Bjerggaard Jensen, Mads Agerbæk, Jakob Skou Pedersen, Lars Dyrskjøt
Analysis of plasma cell-free DNA (cfDNA) may provide important information in cancer research, though the often small fraction of DNA originating from tumor cells makes the analysis technically challenging. Digital droplet PCR (ddPCR) has been utilized extensively as sufficient technical performance is easily achieved, but analysis is restricted to few mutations. Next generation sequencing (NGS) approaches have been optimized to provide comparable technical performance, especially with the introduction of unique identifiers (UIDs)...
January 30, 2018: Scientific Reports
Te-Fu Tsai, Ji-Fan Lin, Kuang-Yu Chou, Yi-Chia Lin, Hung-En Chen, Thomas I-Sheng Hwang
Introduction: miR-99a-5p, known to play an important role in mammalian target of rapamycin (mTOR) regulation, is downregulated in human bladder cancer. The study aimed to investigate the anticancer activity of miR-99a-5p and the possible mechanism associated with mTOR in bladder cancer cells. Materials and methods: Vectors expressing miR-99a-5p were transfected into human urinary bladder urothelial carcinoma (5637 and T24) cells. The level of miR-99a-5p was monitored by microRNA (miRNA) quantitative polymerase chain reaction (QPCR)...
2018: OncoTargets and Therapy
Damiano Fantini, Alexander P Glaser, Kalen J Rimar, Yiduo Wang, Matthew Schipma, Nobish Varghese, Alfred Rademaker, Amir Behdad, Aparna Yellapa, Yanni Yu, Christie Ching-Lin Sze, Lu Wang, Zibo Zhao, Susan E Crawford, Deqing Hu, Jonathan D Licht, Clayton K Collings, Elizabeth Bartom, Dan Theodorescu, Ali Shilatifard, Joshua J Meeks
The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model is an attractive model system of muscle-invasive bladder cancer (MIBC) as it recapitulates the histology of human tumors in a background with intact immune system. However, it was unknown whether this carcinogen-induced model also mimicked human MIBC at the molecular and mutational level. In our study, we analyzed gene expression and mutational landscape of the BBN model by next-generation sequencing followed by a bioinformatic comparison to human MIBC using data from The Cancer Genome Atlas and other repositories...
January 25, 2018: Oncogene
Andrew Butterfield, Sumati Gupta
No abstract text is available yet for this article.
December 2017: Translational Andrology and Urology
Karl H Pang, Francesco Esperto, Aidan P Noon
Bladder cancer (BC) is a common disease in both sexes and majority of cases present as non-muscle invasive BC (NMIBC). The percentage of NMIBC progressing to muscle invasive BC (MIBC) varies between 25% and 75% and currently there are no reliable biomarkers that may predict the outcome of high-risk (HR) NMIBC. Whilst The Cancer Genome Atlas (TCGA) project has identified genetic alteration in MIBC using next-generation sequencing (NGS), genetic data in HR-NMIBC outcome prediction using this new technology are limited...
December 2017: Translational Andrology and Urology
Malte W Vetterlein, Julia Roschinski, Philipp Gild, Phillip Marks, Armin Soave, Ousman Doh, Hendrik Isbarn, Wolfgang Höppner, Walter Wagner, Shahrokh F Shariat, Maurizio Brausi, Franziska Büscheck, Guido Sauter, Margit Fisch, Michael Rink
Background: The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer...
December 2017: Translational Andrology and Urology
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