Article
Genetics & Heredity
Maroun Bou Zerdan, Gennady Bratslavsky, Joseph Jacob, Jeffrey Ross, Richard Huang, Alina Basnet
Summary: This study evaluates the impact of genomic alterations in fibroblast growth factor receptor genes on the response to immune checkpoint inhibitors in urothelial bladder cancer and finds a link between FGFR3 gene alterations and low responsiveness to immune checkpoint inhibitors.
MOLECULAR DIAGNOSIS & THERAPY
(2023)
Article
Oncology
Zechen Wang, Viswanathan Muthusamy, Daniel P. Petrylak, Karen S. Anderson
Summary: Bladder cancer is a common malignancy worldwide, and FGFR3 alterations are frequently found in bladder cancer. The efficacy of FGFR inhibitors is limited, and most patients with FGFR3 fusions still experience relapse. This study discovered the synergistic combination of FGFR and HDAC inhibitors for bladder cancer and provided mechanistic insights. These preclinical studies support the potential translation of this combination therapy to early phase clinical trials.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Stefano Tappero, Andrea Panunzio, Lukas Hohenhorst, Cristina Cano Garcia, Francesco Barletta, Mattia Piccinelli, Zhe Tian, Stefano Parodi, Alessandro Antonelli, Markus Graefen, Felix K. H. Chun, Alberto Briganti, Ottavio De Cobelli, Fred Saad, Shahrokh F. Shariat, Nazareno Suardi, Marco Borghesi, Carlo Terrone, Pierre I. Karakiewicz
Summary: The effect of radical cystectomy (RC) on cancer-specific mortality (CSM) is uncertain in non-metastatic sarcomatoid bladder cancer (SBC) patients. This study aimed to evaluate the benefit of RC in SBC patients and compare it with urothelial bladder cancer (UCB).
Article
Medicine, General & Internal
Rocco Simone Flammia, Antonio Tufano, Francesco Chierigo, Christoph Wurnschimmel, Benedikt Hoeh, Gabriele Sorce, Zhen Tian, Umberto Anceschi, Costantino Leonardo, Francesco Del Giudice, Carlo Terrone, Antonio Giordano, Andrea Morrione, Fred Saad, Shahrokh F. Shariat, Alberto Briganti, Francesco Montorsi, Felix K. H. Chun, Michele Gallucci, Pierre I. Karakiewicz
Summary: Female sex in patients with non-urothelial variant-histology bladder cancer treated with comprehensive radical cystectomy is associated with more advanced stage and worse survival.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biology
Pei-Hang Xu, Siyuan Chen, Yanhao Wang, Shengming Jin, Jun Wang, Dingwei Ye, Xiaodong Zhu, Yijun Shen
Summary: This study investigates the impact of mFGFR3 on the immune status in bladder cancer and the regulation of immune response by FGFR3. The results reveal differential immunity caused by mFGFR3 and the FIPS model effectively predicts prognosis in bladder cancer by identifying patients with diverse immune infiltration and mFGFR3 status in different risk groups.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Oncology
Laura S. Mertens, Francesco Claps, Roman Mayr, Peter J. Bostrom, Shahrokh F. Shariat, Ellen C. Zwarthoff, Joost L. Boormans, Cheno Abas, Geert J. L. H. van Leenders, Stefanie Goetz, Katrin Hippe, Simone Bertz, Yann Neuzillet, Joyce Sanders, Annegien Broeks, Dennis Peters, Michiel S. van der Heijden, Michael A. S. Jewett, Robert Stoehr, Alexandre R. Zlotta, Markus Eckstein, Yanish Soorojebally, Deric K. E. van der Schoot, Bernd Wullich, Maximilian Burger, Wolfgang Otto, Francois Radvanyi, Nanour Sirab, Damien Pouessel, Theo H. van der Kwast, Arndt Hartmann, Yair Lotan, Yves Allory, Tahlita C. M. Zuiverloon, Bas W. G. van Rhijn
Summary: This study analyzed the expression of FGFR3 gene mutation, p53, and Ki-67 in patients with invasive bladder cancer and evaluated their prognostic value. The results showed that FGFR3 gene mutation was associated with lower tumor stage, lower tumor grade, no lymph node metastasis, and longer disease-specific survival. In contrast, abnormal expression of p53 and Ki-67 was only associated with higher tumor stage and G3 grade tumors. Multivariable analysis showed that besides tumor stage, lympho-vascular invasion, and lymph node stage, FGFR3 gene mutation status was a significant predictor of patient prognosis.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2022)
Article
Multidisciplinary Sciences
Alberto Valdes, Athanasios Bitzios, Eszter Kassa, Ganna Shevchenko, Alexander Falk, Per-Uno Malmstrom, Anca Dragomir, Ulrika Segersten, Sara Bergstrom Lind
Summary: Samples preserved by different methods, FFPE and OCT, show differences in protein analysis results using MS technology, with preservation method being a main source of variation. Proteins related to mitochondrial function are overrepresented in OCT data but missing in FFPE data. The use of MS technology for biobank samples is supported and further evaluation of proteins as biomarkers is encouraged.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Aleksander Slusarczyk, Piotr Zapala, Tomasz Piecha, Lukasz Zapala, Tomasz Borkowski, Piotr Radziszewski
Summary: The study found that patients who underwent radical nephroureterectomy for upper urinary tract urothelial cancer after radical cystectomy experienced poor overall survival and cancer-specific survival, with most surgeries being performed for locally advanced tumors. Independent risk factors for worse survival included UTUC T stage, presence of metastasis, and male gender.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Urology & Nephrology
Francesco Claps, Maaike W. van de Kamp, Roman Mayr, Peter J. Bostrom, Shahrokh F. Shariat, Katrin Hippe, Simone Bertz, Yann Neuzillet, Joyce Sanders, Wolfgang Otto, Michiel S. van Der Heijden, Michael A. S. Jewett, Robert Stoehr, Alexandre R. Zlotta, Carlo Trombetta, Markus Eckstein, Laura S. Mertens, Maximilian Burger, Yanish Soorojebally, Bernd Wullich, Riccardo Bartoletti, Francois Radvanyi, Nicola Pavan, Nanour Sirab, M. Carmen Mir, Damien Pouessel, Theo H. van Der Kwast, Arndt Hartmann, Yair Lotan, Rossana Bussani, Yves Allory, Bas W. G. van Rhijn
Summary: The study aims to evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). The results showed that compared to pure urothelial carcinoma, clear-cell, plasmacytoid, small-cell, and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH showed a DSS benefit. Accurate pathological diagnosis can ensure tailored counselling for patients who require more intensive management.
Article
Oncology
Junjie Zhang, Ran Xu, Qiang Lu, Zhenzhou Xu, Jianye Liu, Pei Li, Yaqun Zhang, Chuanchi Zhou, Lufeng Luo, Wei Tang, Zhenting Wang, Manman Cao, Jian Cao, Genming Xu, Long Wang
Summary: In this study, a methylation diagnostic tool using urine sediment was constructed for the detection of urothelial bladder carcinoma (UBC), and the diagnostic performance was improved by incorporating single nucleotide polymorphism sites. The model achieved high sensitivity and specificity, and showed comparable performance to conventional cytology and FISH. It has the potential to be used as a replacement approach for detecting UBC.
Article
Oncology
Richard Naspro, Giovanni La Croce, Marco Finati, Marco Roscigno, Federico Pellucchi, Mario Sodano, Michele Manica, Andrea Gianatti, Luigi F. Da Pozzo
Summary: This study aimed to evaluate the impact of concomitant carcinoma in situ on recurrence and survival outcomes in pure urothelial bladder cancer after radical cystectomy. The results showed that concomitant carcinoma in situ was associated with poorer pathological features and lower recurrence and survival rates compared to pure carcinoma in situ after radical cystectomy. Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants was also associated with higher recurrence rate.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2022)
Article
Oncology
Kenneth Softness, Sumedh Kaul, Aaron Fleishman, Jason Efstathiou, Joaquim Bellmunt, Simon P. Kim, Ruslan Korets, Peter Chang, Andrew Wagner, Aria F. Olumi, Boris Gershman
Summary: In this study, the comparative effectiveness of radical cystectomy (RC) and trimodality therapy (TMT) for muscle-invasive bladder cancer was evaluated using observational data. The results showed no statistically significant difference in overall survival (OS) between RC and TMT. However, when examining heterogeneity of treatment effects, RC appeared to be associated with improved OS only for patients with cT3 disease.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2022)
Article
Oncology
Gottfrid Sjodahl, Pontus Eriksson, Karin Holmsten, Johan Abrahamsson, Mattias Hoglund, Carina Bernardo, Anders Ullen, Fredrik Liedberg
Summary: This study finds that molecular subtypes of urothelial bladder cancer are associated with specific metastatic sites. The Basal/squamous subtype is less likely to metastasize to bone, while the Urothelial-like subtype has an increased tendency to metastasize to bone. The Genomically unstable subtype is less likely to metastasize to the lungs, but is more likely to metastasize to atypical sites, including the brain.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Lucia Schwarzova, Zuzana Varchulova Novakova, Lubos Danisovic, Stanislav Ziaran
Summary: Urothelial bladder carcinoma is one of the top ten most commonly diagnosed cancers worldwide. The classification system based on mRNA expression profiling revealed the existence of molecular subtypes of bladder cancer, which can provide more precise stratification of patients and impact treatment decisions and outcomes.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Immunology
Bingzheng An, Zhaoxin Guo, Junyan Wang, Chen Zhang, Guanghao Zhang, Lei Yan
Summary: Investigating the gene profile, prognosis, and gene mutations related to dendritic cells (DCs) in bladder urothelial carcinoma (BLCA) patients is crucial for identifying sensitivity to immunotherapy. A DC-related risk model was developed to accurately distinguish patients' sensitive responses to immunotherapy and overall survival outcomes. Patients with ryanodine receptor 2 (RYR2) mutation had a better prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Monica P. de Andres, Richard J. Jackson, Irene Felipe, Sladjana Zagorac, Christian Pilarsky, Anna Melissa Schlitter, Jaime Martinez de Villareal, Gun Ho Jang, Eithne Costello, Steve Gallinger, Paula Ghaneh, William Greenhalf, Thomas Knoesel, Daniel H. Palmer, Petra Ruemmele, Wilko Weichert, Markus Buechler, Thilo Hackert, John P. Neoptolemos, Faiyaz Notta, Nuria Malats, Paola Martinelli, Francisco X. Real
Summary: GATA4 and GATA6 cooperate to maintain the classical phenotype in pancreatic ductal adenocarcinoma (PDAC), and their expression is associated with patient prognosis and therapeutic response, providing a theoretical basis for using them as biomarkers of prognosis and therapeutic response.
Review
Pathology
Veronika Bahlinger, Arndt Hartmann, Markus Eckstein
Summary: Genitourinary malignancies comprise various tumor entities with distinct biological characteristics, especially in terms of immunobiology. Immunoreactive tumors like urothelial carcinoma or renal carcinomas have approved immunotherapeutic treatment options, while prostate cancer has low immunogenicity and previous trials did not show survival benefits with immune checkpoint inhibitors.
ADVANCES IN ANATOMIC PATHOLOGY
(2023)
Article
Oncology
Niklas Kluemper, Damian J. Ralser, Joerg Ellinger, Florian Roghmann, Julia Albrecht, Eduard Below, Abdullah Alajati, Danijel Sikic, Johannes Breyer, Christian Bolenz, Friedemann Zengerling, Philipp Erben, Kristina Schwamborn, Ralph M. Wirtz, Thomas Horn, Dora Nagy, Marieta Toma, Glen Kristiansen, Thomas Buettner, Oliver Hahn, Viktor Gruenwald, Christopher Darr, Eva Erne, Steffen Rausch, Jens Bedke, Katrin Schlack, Mahmoud Abbas, Stefanie Zschaebitz, Constantin Schwab, Alexander Mustea, Patrick Adam, Andreas Manseck, Bernd Wullich, Manuel Ritter, Arndt Hartmann, Jurgen Gschwend, Wilko Weichert, Franziska Erlmeier, Michael Hoelzel, Markus Eckstein
Summary: A study on EV treatment for metastatic urothelial carcinoma revealed that membranous NECTIN-4 protein expression significantly decreases during metastatic spread. Absence or weak expression of NECTIN-4 is associated with a significantly shortened progression-free survival on EV treatment, suggesting the importance of determining NECTIN-4 receptor status before initiating EV.
CLINICAL CANCER RESEARCH
(2023)
Article
Genetics & Heredity
Emilie Abby, Stefan C. C. Dentro, Michael W. J. Hall, Joanna C. C. Fowler, Swee Hoe Ong, Roshan Sood, Albert Herms, Gabriel Piedrafita, Irina Abnizova, Christian W. W. Siebel, Moritz Gerstung, Benjamin A. A. Hall, Philip H. H. Jones
Summary: Notch1 mutations have opposite effects in normal and tumor cells of the mouse esophagus. Notch1 blockade reduces premalignant tumor growth and may be used as a prevention strategy for squamous esophageal cancer. NOTCH1 mutant clones are more common in normal human esophagus but less prevalent in esophageal cancers, suggesting that these mutations promote clonal expansion but hinder carcinogenesis. Further experiments confirmed the competitive advantage conferred by Notch1 mutations in mouse esophagus and the potential therapeutic effect of Notch1 blockade in preventing esophageal cancer.
Article
Multidisciplinary Sciences
Miriam Saponaro, Sina Flottmann, Markus Eckstein, Oliver Hommerding, Niklas Kluemper, Dillon Corvino, Sana Hosni, Anja Schmidt, Nicolas Moenig, Doris Schmidt, Joerg Ellinger, Marieta Toma, Glen Kristiansen, Tobias Bald, Andrea Alimonti, Manuel Ritter, Michael Hoelzel, Abdullah Alajati
Summary: The poor prognosis of advanced urothelial carcinoma (UC) and the need for improved treatment have led researchers to investigate the role of CUB domain containing protein 1 (CDCP1) in UC. They found that CDCP1 is highly expressed in advanced UC and its overexpression is associated with shorter overall survival. Experiments with organoids and cell lines demonstrated that CDCP1 plays an oncogenic role by activating the MAPK/ERK pathway and promoting proliferation and migration. Targeting CDCP1 could be a rational therapeutic strategy for advanced UC.
SCIENTIFIC REPORTS
(2023)
Article
Engineering, Biomedical
Cameron Wright, Pietari Makela, Alexandre Bigot, Mikael Anttinen, Peter J. Bostrom, Roberto Blanco Sequeiros
Summary: This study aimed to develop a deep learning model capable of predicting the non-perfused volume (NPV) immediately after prostate ablation therapy without the need for MRI contrast agents. The model was trained and tested using MRI imaging data from 95 patients, and the results showed the feasibility of predicting NPV without the use of MRI contrast agents, which could improve patient treatment outcomes.
BIOMEDICAL ENGINEERING LETTERS
(2023)
Article
Medicine, General & Internal
Alisa Salmivalli, Otto Ettala, Pertti Nurminen, Pekka Kinnala, Peter J. Bostrom, Ville Kyto
Summary: This study aims to compare the short- and long-term risks of PVP and TURP in the treatment of benign prostate enlargement. Retrospective study on consecutive patients in 20 hospitals in Finland showed that PVP had lower postoperative bleeding risk but higher long-term reoperation risk.
ANNALS OF MEDICINE
(2023)
Letter
Urology & Nephrology
Niklas Kluemper, Alexander Cox, Markus Eckstein
Article
Biochemistry & Molecular Biology
Christian Soehngen, David J. Thomas, Margaretha A. Skowron, Felix Bremmer, Markus Eckstein, Anja Stefanski, Marc D. Driessen, Gamal A. Wakileh, Kai Stuehler, Peter Altevogt, Dan Theodorescu, Ruediger Klapdor, Axel Schambach, Daniel Nettersheim
Summary: This study aimed to understand the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of NK cell CAR against CD24 in urological tumor cells. The results showed that CD24 interacts with proteins involved in cell adhesion, ATP binding, phosphoprotein binding, and post-translational modifications. Treatment with NK-CD24-CAR cells significantly decreased cell viability and induced apoptosis specifically in CD24(+) tumor cells. This study provides a promising novel target for immune therapeutic approaches against urological malignancies.
Article
Oncology
Miriam Marques, Sonia Corral, Maria Sanchez-Diaz, Natalia del Pozo, Jaime Martinez de Villarreal, Norbert Schweifer, Ivana Zagorac, Frank Hilberg, Francisco X. Real
Summary: Bladder cancer is a prevalent tumor that requires the development of novel therapies. Nintedanib, an angio-kinase inhibitor, has shown efficacy in combination with chemotherapy for locally advanced muscle-invasive bladder cancer. Our study investigated the mechanisms of action of nintedanib and identified potential markers and treatment strategies to overcome resistance.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Urology & Nephrology
Stella Koutros, Lambertus A. Kiemeney, Parichoy Pal Choudhury, Roger L. Milne, Evangelina Lopez de Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjot, Jonine Figueroa, Diptavo Dutta, Graham G. Giles, Michelle A. T. Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L. McCullough, Neal D. Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K. Cortessis, Margaret R. Karagas, Alison Johnson, Molly R. Schwenn, Dalsu Baris, Helena Furberg, Dean F. Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C. Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A. Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J. Weinstein, Jan G. Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E. Kiltie, Adonina Tardon, Consol Serra, Alfredo Carrato, Reina Garcia-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjonneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H. Vermeulen, K. K. Aben, Tessel E. Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J. Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V. Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C. Stern, Wusheng Yan, Jia Liu, Shengchao Alfred, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A. Wheeler, Mark P. Purdue, Katherine A. McGlynn, Cari M. Kitahara, Christopher A. Haiman, Mark H. Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J. Chanock, Xifeng Wu, Francisco X. Real, Debra T. Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Nuria Malats, Nathaniel Rothman
Summary: A meta-analysis of 32 studies identified novel genetic variants associated with bladder cancer risk and constructed a polygenic risk score (PRS) to stratify lifetime risk. These findings provide insights into the biological underpinnings of bladder cancer and have the potential to inform future preventive strategies.
Article
Pathology
Jacqueline Fontugne, Evanguelos Xylinas, Clementine Krucker, Victoria Dixon, Clarice S. Groeneveld, Ugo Pinar, Gianluigi Califano, Margot Bucau, Jerome Verine, Francois Desgrandchamps, Jean-Francois Hermieu, Francois Radvanyi, Yves Allory, Alexandra Masson-Lecomte
Summary: Through the study of upper tract urothelial carcinomas (UTUCs), we found that the consensus classification can reliably classify UTUCs and highlight intratumoral molecular heterogeneity, with a higher proportion of luminal papillary subtype compared to muscle-invasive bladder cancer (MIBC).
Article
Health Policy & Services
Raymond H. Henderson, Declan French, Elaine Stewart, Dave Smart, Adam Idica, Sandra Redmond, Markus Eckstein, Jordan Clark, Richard Sullivan, Peter Keeling, Mark Lawler
Summary: Precision oncology medicines have lower development and market costs compared to non-precision oncology medicines, and they have a higher return on investment.
JOURNAL OF PHARMACEUTICAL POLICY AND PRACTICE
(2023)
Article
Urology & Nephrology
Bernd Wullich, Helge Taubert, Peter J. Goebell, Torsten Kuwert, Michael Beck, Christian Schott, Andreas S. Baur, Markus Eckstein, Sven Wach
Summary: Significant advancements have been made in personalized medicine, fundamentally changing our conventional comprehension of disease diagnosis and treatment. Next generation sequencing-based molecular testing of tissue and liquid samples has become a pivotal technology in this context. It enables the identification of diagnostic, prognostic, and predictive biomarkers, as well as the improvement of treatment outcomes through targeted therapies and the avoidance of resistant situations.
Review
Biochemistry & Molecular Biology
Maria Ramal, Sonia Corral, Mark Kalisz, Eleonora Lapi, Francisco X. Real
Summary: This study systematically analyzed the transcription factors (TFs) in urothelium and bladder cancer using RNA-Seq and ATAC-Seq data. The results identified known TFs associated with luminal and basal phenotypes, as well as novel candidate TFs involved in bladder cancer and differentiation. Additionally, several TF families were suggested to be involved in urothelial cell differentiation and bladder cancer.