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bladder cancer sequence

Makoto Kawaguchi, Noboru Hara, Vladimir Bilim, Hiroshi Koike, Mituko Suzuki, Tae-Sun Kim, Nan Gao, Yu Dong, Sheng Zhang, Yuji Fujinawa, Osamu Yamamoto, Hiromi Ito, Yoshihiko Tomita, Yuchi Naruse, Akira Sakamaki, Yoko Ishii, Koichi Tsuneyama, Masaaki Inoue, Johbu Itoh, Masanori Yasuda, Nobuo Sakata, Cha-Gyun Jung, Satoshi Kanazawa, Hiroyasu Akatsu, Hiroshi Minato, Takayuki Nojima, Kiyofumi Asai, Yutaka Miura
BACKGROUND: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma...
October 18, 2016: BMC Cancer
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
Joshua J Meeks, Benedito A Carneiro, Sachin G Pai, Daniel T Oberlin, Alfred Rademaker, Kyle Fedorchak, Sohail Balasubramanian, Julia Elvin, Nike Beaubier, Francis J Giles
The genetic mechanisms associated with progression of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have not been described. We conducted selective next-generation sequencing (NGS) of HR-NMIBC and compared the genomic profiles of cancers that responded to intravesical therapy and those that progressed to muscle-invasive or advanced disease. DNA was extracted from paraffin-embedded sections from 25 HR-NMIBCs (22 with T1HG; 3 with TaHG with or without carcinoma in situ). Ten patients with HR-NMIBC developed progression (pT2+ or N+) ("progressors")...
October 14, 2016: Oncotarget
Masaki Kumondai, Hiroki Hosono, Kazuhiko Orikasa, Yoichi Arai, Tomio Arai, Haruhiko Sugimura, Seiichiro Ozono, Takayuki Sugiyama, Tatsuya Takayama, Takamitsu Sasaki, Noriyasu Hirasawa, Masahiro Hiratsuka
Tobacco-specific nitrosamines including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), which can be activated by the metabolic enzyme CYP2A13, are potent procarcinogens. Smoking plays a role in carcinogenesis in the human bladder, which expresses CYP2A13 at a relatively high level. Numerous genetic polymorphisms of CYP2A13 causing amino acid substitution might reduce CYP2A13 metabolic activity toward NNK and NNN, resulting in decreased susceptibility to bladder cancer. The aim of this study was to reveal any association between bladder cancer development and CYP2A13 genetic polymorphisms in Japanese smokers...
2016: Biological & Pharmaceutical Bulletin
Shirou Ishii, Takamitsu Hara, Takeyuki Nanbu, Hiroki Suenaga, Shigeyasu Sugawara, Daichi Kuroiwa, Hirofumi Sekino, Masayuki Miyajima, Hitoshi Kubo, Noboru Oriuchi, Hiroshi Ito
Although PET/MRI has the advantages of a simultaneous acquisition of PET and MRI, high soft-tissue contrast of the MRI images, and reduction of radiation exposure, its low profitability and long acquisition time are significant problems in clinical settings. Thus, MRI protocols that meet oncological purposes need to be used in order to reduce examination time while securing detectability. Currently, half-Fourier acquisition single-shot turbo spin echo and 3D-T1 volumetric interpolated breath-hold examination may be the most commonly used sequences for whole-body imaging due to their shorter acquisition time and higher diagnostic accuracy...
October 6, 2016: Japanese Journal of Radiology
Tuba Avcilar, Deniz Kirac, Deniz Ergec, Gulsah Koc, Korkut Ulucan, Zehra Kaya, Elif Cigdem Kaspar, Levent Turkeri, Ahmet Ilter Guney
Bladder carcinoma is the most common malignancy of the urinary tract. The major aim of the present study is to investigate the association between mitochondrial DNA (mtDNA) and p53 gene mutations in bladder carcinoma. A total of 30 patients with transitional cell carcinoma and 27 controls were recruited for the study. Bladder cancer tissues were obtained by radical cystectomy or transurethral resection. Genomic DNA was extracted from peripheral blood. mtDNA and p53 genes were amplified by polymerase chain reaction and sequenced directly...
October 2016: Oncology Letters
Junjie Zhao, Weidong Xu, Minghui He, Zhensheng Zhang, Shuxiong Zeng, Chong Ma, Yinghao Sun, Chuanliang Xu
Non-muscle-invasive bladder cancer (NMIBC) often has a worse prognosis following its progression to muscle-invasive bladder cancer (MIBC), despite radical cystectomy with pelvic lymph node dissection combined with chemotherapy. Therefore, the discovery of novel biomarkers for predicting the progression of this disease and of therapeutic targets for preventing it is crucial. We performed whole-exome sequencing to analyze superficial tumor tissues (Tsup) and basal tumor tissues (Tbas) from 3 MIBC patients and identified previously unreported copy number variations in IPO11 that warrants further investigation as a molecular target...
September 28, 2016: Oncotarget
J Huang, X Chen, T X Lin
Bladder cancer is one of the most common malignant tumors of the urinary system in China, but it is still difficult to be accurate in the diagnosis and treatment. The rapid development of high-throughput sequencing technology and data analysis of biological information pushes the medicine to enter into the precise times. In the review, the recent progress of molecular subtype, assessment of immune and metastatic status, efficacy prediction of chemotherapy, immunotherapy and targeted therapy are summarized. It provides new ideas and methods for accurate diagnosis and treatment of bladder cancer...
October 1, 2016: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
Maria Frantzi, Zoi Klimou, Manousos Makridakis, Jerome Zoidakis, Agnieszka Latosinska, Daniel M Borràs, Bart Janssen, Ioanna Giannopoulou, Vasiliki Lygirou, Andreas C Lazaris, Nicholas P Anagnou, Harald Mischak, Maria G Roubelakis, Antonia Vlahou
Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet. Earlier studies from our laboratory revealed that decreased tissue levels of Profilin-1 (PFN1) are correlated with BC progression to muscle invasive disease...
September 23, 2016: Oncotarget
S Kuppachi, D Holanda, M Eberlein, B Alexiev, A J Tyler, M C Wissel, S B Kleiboeker, C P Thomas
We report a lung transplant recipient who developed BK polyoma virus (BKPyV) DNAemia and BKPyV nephropathy. With careful management of his immunosuppression he achieved significant reduction in BKPyV DNAemia and stabilization of his kidney function. He later developed a high-grade bladder cancer and shortly thereafter he experienced a major upsurge in the level of BKPyV DNAemia that coincided with the discovery of hepatic metastasis. Retrospectively, the bladder cancer and the hepatic secondary tumor stained uniformly for SV40 large T antigen, and the BKPyV DNA sequences identified in plasma corresponded to BKPyV DNA within hepatic tissue, indicating that the spike in BKPyV load was likely derived from the circulating tumor cells or cell-free tumor DNA following metastases of a BKV-associated cancer...
September 20, 2016: American Journal of Transplantation
Evanguelos Xylinas, Melanie R Hassler, Dazhong Zhuang, Martin Krzywinski, Zeynep Erdem, Brian D Robinson, Olivier Elemento, Thomas Clozel, Shahrokh F Shariat
Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients...
September 2, 2016: Biomolecules
Mathilde B H Thomsen, Iver Nordentoft, Philippe Lamy, Søren Høyer, Søren Vang, Jakob Hedegaard, Michael Borre, Jørgen B Jensen, Torben F Ørntoft, Lars Dyrskjøt
Patients with metastatic bladder cancer have a median survival of only 13-14 months. Precision medicine using targeted therapy may improve survival. Here we investigated spatial and temporal tumour evolution and tumour heterogeneity in order to evaluate the potential use of targeted treatment of metastatic bladder cancer. We performed a proof-of-concept study by whole exome sequencing of multiple tumour regions (n = 22) from three patients with metastatic bladder cancer. DNA from primary and metastatic tumour biopsies was analysed for mutations using Mutect and potential therapeutic targets were identified...
November 2016: Molecular Oncology
Jinwoo Ahn, Kwang Hyun Kim, Sanghui Park, Young-Ho Ahn, Ha Young Kim, Hana Yoon, Ji Hyun Lee, Duhee Bang, Dong Hyeon Lee
UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66...
August 11, 2016: Oncotarget
Thomas Longo, Kathleen F McGinley, Jennifer A Freedman, Wiguins Etienne, Yuan Wu, Alexander Sibley, Kouros Owzar, Jeremy Gresham, Christopher Moy, Stephen Szabo, Joel Greshock, Hui Zhou, Yuchen Bai, Brant A Inman
: We completed targeted exome sequencing of the tumors of 50 patients with pTis-pT4b bladder cancer. Mutations were categorized by type, stratified against previously identified cancer loci in the Catalogue of Somatic Mutations in Cancer and The Cancer Genome Atlas databases, and evaluated in pathway analysis and comutation plots. We analyzed mutation associations with receipt of neoadjuvant chemotherapy, nodal involvement, metastatic disease development, and survival. Compared with The Cancer Genome Atlas, we found higher mutation rates in genes encoding products involved in epigenetic regulation and cell cycle regulation...
August 9, 2016: European Urology
Jean Hoffman-Censits, Lindsay Wilde
PURPOSE OF REVIEW: Combination immunotherapy has already shown promise in several tumor types, such as melanoma and nonsmall cell lung cancer, and studies are ongoing to evaluate this approach in other malignancies. Trials such as these will only continue to expand as additional immune therapies are shown to have efficacy as single agents in cancer. The purpose of this review is to outline the current landscape of immunotherapy in genitourinary cancer, and to highlight ongoing and pending combination immunotherapy trials in bladder, kidney, and prostate cancers...
November 2016: Current Opinion in Urology
Romina D'Aurizio, Tommaso Pippucci, Lorenzo Tattini, Betti Giusti, Marco Pellegrini, Alberto Magi
Copy Number Variants (CNVs) are structural rearrangements contributing to phenotypic variation that have been proved to be associated with many disease states. Over the last years, the identification of CNVs from whole-exome sequencing (WES) data has become a common practice for research and clinical purpose and, consequently, the demand for more and more efficient and accurate methods has increased. In this paper, we demonstrate that more than 30% of WES data map outside the targeted regions and that these reads, usually discarded, can be exploited to enhance the identification of CNVs from WES experiments...
August 9, 2016: Nucleic Acids Research
Andre Kunert, Mandy van Brakel, Sabine van Steenbergen-Langeveld, Marvin da Silva, Pierre G Coulie, Cor Lamers, Stefan Sleijfer, Reno Debets
Adoptive T cell therapy has shown significant clinical success for patients with advanced melanoma and other tumors. Further development of T cell therapy requires improved strategies to select effective, yet nonself-reactive, TCRs. In this study, we isolated 10 TCR sequences against four MAGE-C2 (MC2) epitopes from melanoma patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. We introduced these TCRs into T cells, pretreated tumor cells of different histological origins with the epigenetic drugs azacytidine and valproate, and tested tumor and self-reactivities of these TCRs...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Philippe Lamy, Iver Nordentoft, Karin Birkenkamp-Demtröder, Mathilde Borg Houlberg Thomsen, Palle Villesen, Søren Vang, Jakob Hedegaard, Michael Borre, Jørgen Bjerggaard Jensen, Søren Høyer, Jakob Skou Pedersen, Torben F Ørntoft, Lars Dyrskjøt
Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations...
October 1, 2016: Cancer Research
Gabriel G Malouf, Eva Compérat, Hui Yao, Roger Mouawad, Veronique Lindner, Nathalie Rioux-Leclercq, Virginie Verkarre, Xavier Leroy, Linda Dainese, Marion Classe, Jean-Luc Descotes, Philippe Barthelemy, Mokrane Yacoub, Morgan Rouprêt, Jean-Christophe Bernhard, Chad J Creighton, Jean-Philippe Spano, Xiaoping Su, David Khayat
Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Herein, we performed for the first time transcriptome sequencing of CDC and compared them to UTUC and renal cell carcinoma subtypes. We discovered that CDC displays a unique transcriptomic signature among kidney cancer subtypes, with a putative cell of origin in the distal convoluted tubules...
2016: Scientific Reports
Neil B Desai, Sasinya N Scott, Emily C Zabor, Eugene K Cha, Joseph Hreiki, John P Sfakianos, Ricardo Ramirez, Aditya Bagrodia, Jonathan E Rosenberg, Dean F Bajorin, Michael F Berger, Bernard H Bochner, Michael J Zelefsky, Marisa A Kollmeier, Irina Ostrovnaya, Hikmat A Al-Ahmadie, David B Solit, Gopa Iyer
BACKGROUND: The authors characterized the genetic landscape of chemoradiation-treated urothelial carcinoma of the bladder (UCB) with the objective of identifying potential correlates of response. METHODS: Primary tumors with (n = 8) or without (n = 40) matched recurrent tumors from 48 patients who had non-metastatic, high-grade UCB and received treatment primarily with chemoradiation were analyzed using a next-generation sequencing assay enriched for cancer-related and canonical DNA damage response (DDR) genes...
August 1, 2016: Cancer
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