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https://www.readbyqxmd.com/read/27896485/biomarkers-for-precision-medicine-in-bladder-cancer
#1
REVIEW
Takahiro Kojima, Koji Kawai, Jun Miyazaki, Hiroyuki Nishiyama
Bladder cancer (BC) is classified as non-muscle-invasive BC (NMIBC) or muscle-invasive BC (MIBC). Because the recurrence and mortality rates of BC are high, suitable biomarkers for early detection, evaluation of prognosis, and surveillance of drug responses are needed. Urinary markers simplify surveillance schedules and improve early detection of tumors, especially in NMIBC. Various markers have been identified at DNA, RNA, and protein levels with different sensitivities and specificities. Several biomarkers show a higher sensitivity than urinary cytology, but they are not accurate enough to replace it...
November 29, 2016: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#2
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27836246/emerging-role-of-immunotherapy-in-urothelial-carcinoma-immunobiology-biomarkers
#3
REVIEW
Randy F Sweis, Matthew D Galsky
Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette-Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement...
December 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27823983/genomic-profiling-is-predictive-of-response-to-cisplatin-treatment-but-not-to-pi3k-inhibition-in-bladder-cancer-patient-derived-xenografts
#4
Lei Wei, Sreenivasulu Chintala, Eric Ciamporcero, Swathi Ramakrishnan, May Elbanna, Jianmin Wang, Qiang Hu, Sean T Glenn, Mitsuko Murakami, Lu Liu, Eduardo Cortes Gomez, Yuchen Sun, Jacob Conroy, Kiersten Marie Miles, Kullappan Malathi, Sudha Ramaiah, Anand Anbarasu, Anna Woloszynska-Read, Candace S Johnson, Jeffrey Conroy, Song Liu, Carl D Morrison, Roberto Pili
PURPOSE: Effective systemic therapeutic options are limited for bladder cancer. In this preclinical study we tested whether bladder cancer gene alterations may be predictive of treatment response. EXPERIMENTAL DESIGN: We performed genomic profiling of two bladder cancer patient derived tumor xenografts (PDX). We optimized the exome sequence analysis method to overcome the mouse genome interference. RESULTS: We identified a number of somatic mutations, mostly shared by the primary tumors and PDX...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27807073/archetype-and-rearranged-non-coding-control-regions-in-urothelial-bladder-carcinoma-of-immunocompetent-individuals
#5
Elena Anzivino, Maria Antonella Zingaropoli, Marco Iannetta, Valeria Antonietta Pietropaolo, Alessandra Oliva, Francesco Iori, Antonio Ciardi, Donatella Maria Rodio, Francesca Antonini, Cesare Giovanni Fedele, Alessandra D'Abramo, Claudio Maria Mastroianni, Vincenzo Vullo, Maria Rosa Ciardi
BACKGROUND: Polyomaviruses (PyVs) are potential transforming viruses. Despite their involvement in human tumours still being debated, there is evidence to suggest a role for PyVs in bladder carcinoma (BC). Therefore, a possible association between PyVs and BC was investigated. MATERIALS AND METHODS: Urine, blood and fresh bladder tissue specimens were collected from 29 patients with BC. PyV prevalence, non-coding control region (NCCR) organization and genotypic analysis were assessed...
November 2016: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27784990/molecular-targets-in-urothelial-cancer-detection-treatment-and-animal-models-of-bladder-cancer
#6
REVIEW
Dmitriy Smolensky, Kusum Rathore, Maria Cekanova
Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27774692/isolation-and-partial-characterization-of-3-nontoxic-d-galactose-specific-isolectins-from-seeds-of-momordica-balsamina
#7
Amna K E Awadallah, Makarim Elfadil M Osman, Mariam A Ibrahim, Emerson S Bernardes, Marcelo Dias-Baruffi, Emadeldin Hassan E Konozy
Three isolectins denoted hereforth MBaL-30, MBaL-60, and MBaL-80 were isolated from seeds extract of Momordica balsamina by 30%, 60%, and 80% ammonium sulfate saturations, respectively. The native molecular weights of these lectins, as judged by gel filtration, were 108, 56, and 160 kDa, respectively. On SDS-PAGE, under reduced condition, 27 kDa band was obtained for all isolectins. The lectins hemagglutinating activities were variably inhibited by d-galactose (minimum inhibitory concentrations = 12.5mM, 50mM, and 0...
October 24, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27756245/a-diagnostic-marker-for-superficial-urothelial-bladder-carcinoma-lack-of-nuclear-atbf1-zfhx3-by-immunohistochemistry-suggests-malignant-progression
#8
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
https://www.readbyqxmd.com/read/27751785/circulating-biomarkers-to-guide-systemic-therapy-for-urothelial-carcinoma
#9
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
https://www.readbyqxmd.com/read/27750214/genomic-characterization-of-high-risk-non-muscle-invasive-bladder-cancer
#10
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
https://www.readbyqxmd.com/read/27725446/cyp2a13-genetic-polymorphisms-in-relation-to-the-risk-of-bladder-cancer-in-japanese-smokers
#11
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
https://www.readbyqxmd.com/read/27714486/optimized-workflow-and-imaging-protocols-for-whole-body-oncologic-pet-mri
#12
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
https://www.readbyqxmd.com/read/27698873/investigation-of-the-association-between-mitochondrial-dna-and-p53-gene-mutations-in-transitional-cell-carcinoma-of-the-bladder
#13
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
https://www.readbyqxmd.com/read/27689332/whole-exome-sequencing-of-muscle-invasive-bladder-cancer-identifies-recurrent-copy-number-variation-in-ipo11-and-prognostic-significance-of-importin-11-overexpression-on-poor-survival
#14
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
https://www.readbyqxmd.com/read/27686634/-strategies-for-diagnosis-and-treatment-of-bladder-cancer-in-precise-times
#15
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]
https://www.readbyqxmd.com/read/27683119/silencing-of-profilin-1-suppresses-cell-adhesion-and-tumor-growth-via-predicted-alterations-in-integrin-and-ca2-signaling-in-t24m-based-bladder-cancer-models
#16
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
https://www.readbyqxmd.com/read/27647675/an-unexpected-surge-in-plasma-bkpyv-viral-load-heralds-the-development-of-bkpyv-associated-metastatic-bladder-cancer-in-a-lung-transplant-recipient-with-bkpyv-nephropathy
#17
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
https://www.readbyqxmd.com/read/27598218/an-epigenomic-approach-to-improving-response-to-neoadjuvant-cisplatin-chemotherapy-in-bladder-cancer
#18
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
https://www.readbyqxmd.com/read/27582092/spatial-and-temporal-clonal-evolution-during-development-of-metastatic-urothelial-carcinoma
#19
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
https://www.readbyqxmd.com/read/27533081/target-sequencing-and-crispr-cas-editing-reveal-simultaneous-loss-of-utx-and-uty-in-urothelial-bladder-cancer
#20
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
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