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https://www.readbyqxmd.com/read/28927152/expression-levels-of-fgfr3-as-a-prognostic-marker-for-the-progression-of-primary-pt1-bladder-cancer-and-its-association-with-mutation-status
#1
Ho Won Kang, Ye-Hwan Kim, Pildu Jeong, Cheol Park, Won Tae Kim, Dong Hee Ryu, Eun-Jong Cha, Yun-Sok Ha, Tae-Hwan Kim, Tae Gyun Kwon, Sung-Kwon Moon, Yung Hyun Choi, Seok-Joong Yun, Wun-Jae Kim
The present study examined the utility of fibroblast growth factor receptor 3 (FGFR3) mutation status and gene expression as a prognostic marker in primary pT1 bladder cancer (BC). A total of 120 patients with primary pT1 BC were enrolled. FGFR3 mutation status was determined by direct sequencing and FGFR3 mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The results were compared with the clinicopathological parameters, and the prognostic value of FGFR3 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression test...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28917596/response-rate-to-chemotherapy-after-immune-checkpoint-inhibition-in-metastatic-urothelial-cancer
#2
Bernadett Szabados, Nick van Dijk, Yen Zhi Tang, Michiel van der Heijden, Akhila Wimalasingham, Alfonso Gomez de Liano, Simon Chowdhury, Simon Hughes, Sarah Rudman, Mark Linch, Thomas Powles
Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described (n=28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1...
September 13, 2017: European Urology
https://www.readbyqxmd.com/read/28916750/comprehensive-multiregional-analysis-of-molecular-heterogeneity-in-bladder-cancer
#3
Mathilde Borg Houlberg Thomsen, Iver Nordentoft, Philippe Lamy, Søren Vang, Line Reinert, Christophe Kamungu Mapendano, Søren Høyer, Torben F Ørntoft, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#4
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28903380/mex3a-expression-and-survival-analysis-of-bladder-urothelial-carcinoma
#5
Jing-Wen Shi, Ying Huang
OBJECTIVE: Bladder urothelial carcinoma is a common tumor in humans and a multifactorial disease. The gene mex3a is associated with tumor formation and may promote cell proliferation and migration. Therefore, this study aimed to determine the relationship between mex3a and bladder urothelial carcinoma. METHODS: The clinical and RNA sequencing expression data in patients with bladder urothelial carcinoma were downloaded from the The Cancer Genome Atlas data portal...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28889380/detection-of-apobec3-proteins-and-catalytic-activity-in-urothelial-carcinoma
#6
Ananda Ayyappan Jaguva Vasudevan, Wolfgang Goering, Dieter Häussinger, Carsten Münk
Members of the APOBEC3 (A3) family of enzymes were shown to act in an oncogenic manner in several cancer types. Immunodetection of APOBEC3A (A3A), APOBEC3B (A3B), and APOBEC3G (A3G) proteins is particularly challenging due to the large sequence homology of these proteins and limited availability of antibodies. Here we combine independent immunoblotting with an in vitro activity assay technique, to detect and categorize specific A3s expressed in urothelial bladder cancer and other cancer cells.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28832261/prospects-and-progress-of-immunotherapy-for-bladder-cancer
#7
Martin Boegemann, Ahmet Murat Aydin, Aditya Bagrodia, Laura-Maria Krabbe
With recent advances in immunooncology and the introduction of checkpoint inhibitors into clinical practice for many cancers, the treatment landscape of urothelial carcinoma has changed dramatically and will continue to change further. Currently, a number of compounds and combinations are under investigation in numerous clinical trials and various clinical scenarios for bladder cancer. Areas covered: In this review, the authors provide an overview of the history and rationale for immunotherapy in bladder cancer...
August 23, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28827400/upf1-helicase-promotes-tsn-mediated-mirna-decay
#8
Reyad A Elbarbary, Keita Miyoshi, Omar Hedaya, Jason R Myers, Lynne E Maquat
While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of miRNAs that contain CA and/or UA dinucleotides. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, we report here that cellular TumiD requires UPF1...
July 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28815048/society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-bladder-carcinoma
#9
Ashish M Kamat, Joaquim Bellmunt, Matthew D Galsky, Badrinath R Konety, Donald L Lamm, David Langham, Cheryl T Lee, Matthew I Milowsky, Michael A O'Donnell, Peter H O'Donnell, Daniel P Petrylak, Padmanee Sharma, Eila C Skinner, Guru Sonpavde, John A Taylor, Prasanth Abraham, Jonathan E Rosenberg
The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#10
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28807024/society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-bladder-carcinoma
#11
Ashish M Kamat, Joaquim Bellmunt, Matthew D Galsky, Badrinath R Konety, Donald L Lamm, David Langham, Cheryl T Lee, Matthew I Milowsky, Michael A O'Donnell, Peter H O'Donnell, Daniel P Petrylak, Padmanee Sharma, Eila C Skinner, Guru Sonpavde, John A Taylor, Prasanth Abraham, Jonathan E Rosenberg
The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28802562/current-research-development-of-single-cell-genome-in-urological-tumor
#12
Ziyi Cao, Song Wu
The technique of whole genome amplification is advancing rapidly and generating attention on detecting genomic lesions in individual cancer cells. Also, single-cell genome could label the uniqueness of each cell, its individual mutations and structural variations especially in cancer studies. In this Review, we provide the insight into the current state of single-cell genome in urological tumor mainly including kidney cancer, bladder cancer and prostate cancer. We put more forward on the new progress of the technique used by single-cell genomes and different results of the genes transform on random tumor tissue from single cell isolated on account of tumor heterogeneity...
August 9, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28775129/comprehensive-molecular-profiling-of-olfactory-neuroblastoma-identifies-potentially-targetable-fgfr3-amplifications
#13
Lorena Lazo de la Vega, Jonathan B McHugh, Andi K Cani, Komal Kunder, Frances M Walocko, Chia-Jen Liu, Daniel H Hovelson, Dan R Robinson, Arul M Chinnaiyan, Scott A Tomlins, Paul W Harms
Olfactory neuroblastomas (ONBs), also known as esthesioneuroblastomas, are malignant round-cell tumors that represent up to 5% of sinonasal malignancies. Despite their aggressive course, molecular studies of ONBs have been limited, and targeted therapies are lacking. To identify potential oncogenic drivers and targetable pathways in ONBs, we characterized 20 ONBs, including archived ONBs profiled by targeted, multiplexed PCR (mxPCR) based DNA next generation sequencing (NGS) of the coding sequence of over 400 cancer-relevant genes (n=16), mxPCR based RNA NGS of 108 target genes (n=15), and two ONBs profiled by comprehensive hybrid-capture based clinical grade NGS of >1,500 genes...
August 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28760909/-span-style-font-weight-400-circulating-tumor-dna-reveals-clinically-actionable-somatic-genome-of-metastatic-bladder-cancer-span
#14
Gillian R Vandekerkhove, Tilman Todenhöfer, Matti Annala, Werner J Struss, Amanda Wong, Kevin Beja, Elie Ritch, Sonal Brahmbhatt, Stas Volik, Jörg Hennenlotter, Matti Nykter, Kim N Chi, Scott North, Arnulf Stenzl, Colin C Collins, Bernhard J Eigl, Peter C Black, Alexander W Wyatt
Targeted agents and immunotherapies promise to transform the treatment of metastatic bladder cancer (BCa), but therapy selection will depend on practical tumor molecular stratification. Circulating tumor DNA (ctDNA) is established in several solid malignancies as a minimally-invasive tool to profile the tumor genome in real-time, but is critically under-explored in BCa. <p>Experimental Design: We applied a combination of whole exome sequencing and targeted sequencing across 50 BCa driver genes to plasma cell-free DNA (cfDNA) from 51 patients with aggressive BCa, including 37 with metastatic disease...
July 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28745580/pharmacogenomic-considerations-in-the-treatment-of-muscle-invasive-bladder-cancer
#15
Tahlita Cm Zuiverloon, Dan Theodorescu
Recent advances in next-generation sequencing techniques have greatly improved our understanding of the genomic alterations in bladder cancer. Cisplatin-based chemotherapy provides a viable treatment option in the neoadjuvant, adjuvant and metastatic setting in a selected group of patients, but chemoresistance is a major problem. The underlying mechanisms of treatment resistance are poorly understood and elucidating these pathways will subsequently lead to improved patient selection, less unnecessary drug-related toxicity, improved patient outcome and decreased healthcare costs...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28723478/low-t-cell-receptor-diversity-high-somatic-mutation-burden-and-high-neoantigen-load-as-predictors-of-clinical-outcome-in-muscle-invasive-bladder-cancer
#16
Noura J Choudhury, Kazuma Kiyotani, Kai Lee Yap, Alexa Campanile, Tatjana Antic, Poh Yin Yew, Gary Steinberg, Jae Hyun Park, Yusuke Nakamura, Peter H O'Donnell
BACKGROUND: The success of cancer immunotherapies has highlighted the potent ability of local adaptive immune responses to eradicate cancer cells by targeting neoantigens generated by somatic alterations. However, how these factors interact to drive the natural history of muscle-invasive bladder cancer (MIBC) is not well understood. OBJECTIVE: To investigate the role of immune regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing of tumor-infiltrating T cells (TILs), in silico neoantigen prediction from exome sequences, and expression analysis of immune-related genes...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28719349/identification-of-g2607a-mutation-in-egfr-gene-with-a-significative-rate-in-moroccan-patients-with-bladder-cancer
#17
W El Hamdani, K Hadami, M Bensaid, H El Ahanidi, A Ameur, A Filali Maltouf, M Abbar, M Attaleb, A Albouzidi, M El Mzibri
The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28717136/association-of-plasma-and-urinary-mutant-dna-with-clinical-outcomes-in-muscle-invasive-bladder-cancer
#18
K M Patel, K E van der Vos, C G Smith, F Mouliere, D Tsui, J Morris, D Chandrananda, F Marass, D van den Broek, D E Neal, V J Gnanapragasam, T Forshew, B W van Rhijn, C E Massie, N Rosenfeld, M S van der Heijden
Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve a 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, from 17 patients undergoing NAC. We assessed single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706610/a-novel-variant-of-oct4-entitled-oct4b3-is-expressed-in-human-bladder-cancer-and-astrocytoma-cell-lines
#19
Ensieh M Poursani, Majid Mehravar, Bahram Mohammad Soltani, Seyed Javad Mowla, James E Trosko
BACKGROUND: Alternative splicing is an important mechanism that regulates gene expression and function in human cells. OCT4, a crucial pluripotency marker in embryonic stem/carcinoma cells generates several spliced variants in different cell types and cancers. The expression of OCT4 in cancers has been challenged in many studies. The existence of several OCT4 spliced variants and absence of specific discriminating primers is the main reason of this controversy. Therefore, using specific primers and discriminating OCT4 variants from each other might help to reduce these discrepancies in carcinogenesis and stem cell researches...
July 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28705507/dosimetric-comparison-of-rapidplan-and-manually-optimized-plans-in-volumetric-modulated-arc-therapy-for-prostate-cancer
#20
Kazuki Kubo, Hajime Monzen, Kentaro Ishii, Mikoto Tamura, Ryu Kawamorita, Iori Sumida, Hirokazu Mizuno, Yasumasa Nishimura
PURPOSE: This study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer. METHODS: We used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D95%, and D2% to planning target volume (PTV), mean dose, V50Gy, V70Gy, V75Gy, and V78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity...
July 10, 2017: Physica Medica: PM
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