Article
Medicine, Research & Experimental
A. C. Nickel, D. Picard, N. Qin, M. Wolter, K. Kaulich, M. Hewera, D. Pauck, V Marquardt, G. Torga, S. Muhammad, W. Zhang, O. Schnell, H-J Steiger, D. Haenggi, E. Fritsche, N-G Her, D-H Nam, M. S. Carro, M. Remke, G. Reifenberger, U. D. Kahlert
Summary: Longitudinal epigenetic and transcriptional profiling of glioblastoma spheroid cell lines demonstrated their molecular stability and reproducible drug responses over prolonged culture times. Integration of gene expression and drug response data revealed predictive gene signatures linked to drug sensitivity, suggesting the potential of predicting glioblastoma therapy response based on gene expression. The study highlights the usefulness of glioblastoma spheroid disease modeling as a preclinical assay to uncover novel therapeutic vulnerabilities and associated molecular alterations.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Devin G. Roller, Stephen A. Hoang, Kristopher D. Rawls, Katherine A. Owen, Michael B. Simmers, Robert A. Figler, Julia D. Wulfkuhle, Emanuel F. Petricoin, Brian R. Wamhoff, Daniel Gioeli
Summary: The study demonstrated the utility of tumor microenvironment system (TMES) in predicting drug response to EGFR inhibitors for non-small cell lung cancer (NSCLC) patients, showcasing its ability to recapitulate in vivo biological state and provide a powerful tool for drug development.
SCIENTIFIC REPORTS
(2021)
Review
Biochemical Research Methods
Fangfang Xia, Jonathan Allen, Prasanna Balaprakash, Thomas Brettin, Cristina Garcia-Cardona, Austin Clyde, Judith Cohn, James Doroshow, Xiaotian Duan, Veronika Dubinkina, Yvonne Evrard, Ya Ju Fan, Jason Gans, Stewart He, Pinyi Lu, Sergei Maslov, Alexander Partin, Maulik Shukla, Eric Stahlberg, Justin M. Wozniak, Hyunseung Yoo, George Zaki, Yitan Zhu, Rick Stevens
Summary: To enable personalized cancer treatment, machine learning models have been developed to predict drug response based on tumor and drug features. This study used machine learning to analyze five publicly available cell line-based data sets and rigorously evaluated the model generalizability between different studies. The results showed that a multitasking deep neural network achieved the best cross-study generalizability, with models trained on the CTRP data set providing the most accurate predictions on testing data, and the gCSI data set being the most predictable among the cell line data sets.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Andrea Holickova, Jan Roska, Eveline Orasova, Vladimira Bruderova, Patrik Palacka, Dana Jurkovicova, Miroslav Chovanec
Summary: Cisplatin-based chemotherapy is commonly used for muscle-invasive bladder cancer, but many cases develop resistance or do not respond. This study found that the response to cisplatin in urothelial carcinoma cells is dependent on DNA damage repair and tolerance factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Lucia Trastulla, Javad Noorbakhsh, Francisca Vazquez, James McFarland, Francesco Iorio
Summary: Immortal cancer cell lines (CCLs) are widely used in cancer biology research and preclinical development of oncology therapies. However, there are limitations to using CCLs as tumor proxies, and it is important to develop more accurate in vitro models. This article discusses the limitations of CCLs and reviews computational methods for evaluating their suitability as tumor proxies, as well as identifying the best in vitro patient representative models.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Phong B. H. Nguyen, Alexander J. Ohnmacht, Samir Sharifli, Mathew J. Garnett, Michael P. Menden
Summary: This study highlights the impact of genetic ancestry on drug response in cancer patients. Differential drug responses were found between European and East Asian ancestries, especially when treated with PI3K/mTOR inhibitors, emphasizing the importance of considering germline landscape in precision medicine to reduce clinical trial failure rates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Silvia Cascianelli, Chiara Barbera, Alexandra Ambra Ulla, Elena Grassi, Barbara Lupo, Diego Pasini, Andrea Bertotti, Livio Trusolino, Enzo Medico, Claudio Isella, Marco Masseroli
Summary: Transcriptional classification of colorectal cancer (CRC) can stratify it into molecular subtypes with distinct biological and clinical features. However, it is unclear if these subtypes are discrete entities or states with potential overlap. This study focused on the CRC Intrinsic Subtype (CRIS) classifier and evaluated whether assigning multiple CRIS subtypes to the same sample provides additional clinically and biologically relevant information.
Article
Biochemical Research Methods
Grant R. Howard, Tyler A. Jost, Thomas E. Yankeelov, Amy Brock
Summary: In this study, a method of optimizing drug schedules in vitro through iterative application of experimentally calibrated models is presented. The study demonstrates the ability to characterize dynamic changes in sensitivity to the chemotherapeutic doxorubicin in breast cancer cell lines. The findings show that the inter-treatment interval is a key variable in determining the performance of sequential dosing schedules, allowing for optimization of drug scheduling.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Genetics & Heredity
Edward Simpson, Steven Chen, Jill L. Reiter, Yunlong Liu
Summary: This study evaluated the potential of using basal-level splicing information to predict drug sensitivity by constructing classification models with splicing and expression data. The researchers detailed splicing differences between sensitive and resistant cell lines, identified altered inclusion of 277 skipped exons, and characterized potential cis- and trans-acting elements influencing doxorubicin response. The results showed a strong predictive power of the classification model built with skipped exon data, revealing an association with epithelial-mesenchymal transition and differential expression of RBFOX and ELAVL RBP family members.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2021)
Article
Biochemical Research Methods
Alexander Partin, Thomas Brettin, Yvonne A. Evrard, Yitan Zhu, Hyunseung Yoo, Fangfang Xia, Songhao Jiang, Austin Clyde, Maulik Shukla, Michael Fonstein, James H. Doroshow, Rick L. Stevens
Summary: The study evaluates and compares the data scaling properties of two neural networks and two gradient boosting decision tree models on four cell line drug screening datasets. The findings suggest that the multi-input neural network outperforms single-input neural networks at higher training sizes, while gradient boosting decision tree exhibits superior performance at the lower range of training set sizes for two datasets. Increasing the sample size is expected to further improve prediction scores of both neural networks.
BMC BIOINFORMATICS
(2021)
Article
Immunology
Hui Fang, Shuyan Sheng, Bangjie Chen, Jianpeng Wang, Deshen Mao, Yanxun Han, Yuchen Liu, Xinyi Wang, Siyu Gui, Tongyuan Zhang, Lizhi Zhang, Conghan Li, Xinyang Hu, Wanyu Deng, Xin Liu, Honghai Xu, Wentao Xu, Xingyu Wang, Rongqiang Liu, Weihao Kong
Summary: This study unraveled the oncogenic role of CDCA4 in different cancers and investigated its correlation with tumor immune infiltration and prognosis from the perspective of tumor immunity, providing new insights for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pathology
Florestan J. Koll, Claudia Doering, Leon Herwig, Benedikt Hoeh, Mike Wenzel, Cristina Cano Garcia, Severine Banek, Luis Kluth, Jens Koellermann, Andreas Weigert, Felix K-H Chun, Peter Wild, Henning Reis
Summary: Consensus molecular subtypes can help stratify patients with MIBC. Luminal tumors have better prognosis and less benefit from adjuvant chemotherapy compared with Ba/Sq tumors.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Weizhi Chen, Yang Yuan, Cheng Li, Hui Mao, Baorui Liu, Xiqun Jiang
Summary: This study reveals that blocking cancer cell signaling can disrupt tumor extracellular matrix, and it is demonstrated that multireceptor-mediated modulation of tumor ECM can reverse tumor microenvironment remodeling. These findings are not only important for understanding the regulatory role of cancer cells in tumor microenvironment development, but also introduce a new therapeutic platform or strategy for cancer treatment.
ADVANCED MATERIALS
(2022)
Article
Oncology
Miok Kim, Yong Ki Min, Jinho Jang, Hyejin Park, Semin Lee, Chang Hoon Lee
Summary: This study reveals the distinct immune modulation effects of CD73 inhibition compared to PD-1 blockade, suggesting that AB680 may serve as a novel anticancer immunotherapy for CRC with potential synergistic effects when combined with PD-1 blockers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemical Research Methods
Akram Emdadi, Changiz Eslahchi
Summary: Predicting tumor drug response using cancer cell line drug response values is a significant challenge in personalized medicine. The TCLMF method, based on gene expression profiles, tissue type information, drug chemical structure, and drug sensitivity data, is proposed as a predictive model for drug response in tumor samples. The method shows accurate predictions and effective latent vectors for tumor samples.
JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY
(2022)
Review
Urology & Nephrology
Michael Nazmifar, Cheyenne Williams, Aurash Naser-Tavakolian, John Heard, Charles Rosser, Dan Theodorescu, Michael Ahdoot
Summary: The purpose of this study is to evaluate the efficacy of various therapeutic agents for high-grade nonmuscle-invasive bladder cancer following failed bacillus Calmette-Guerin treatment. A systematic review of available clinical trials was conducted, and a total of 70 studies evaluating 27 treatment options were analyzed. Intravesical chemotherapy and hyperthermia paired with chemotherapy demonstrated high complete response rates, while immunotherapy and novel agents also showed promising results. The treatments had low toxicity profiles and complication rates.
JOURNAL OF UROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Song Wu, Yue Huang, Mochen Zhang, Zheng Gong, Guoliang Wang, Xinchang Zheng, Wenting Zong, Wei Zhao, Peiqi Xing, Rujiao Li, Zhaoqi Liu, Yiming Bao
Summary: ASCancer Atlas is a comprehensive knowledgebase of aberrant splicing in human cancers, providing a high-confidence collection of cancer-associated splicing events, a systematic splicing regulatory network, computationally putative splicing events, and online analysis tools.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mochen Zhang, Wenting Zong, Dong Zou, Guoliang Wang, Wei Zhao, Fei Yang, Song Wu, Xinran Zhang, Xutong Guo, Yingke Ma, Zhuang Xiong, Zhang Zhang, Yiming Bao, Rujiao Li
Summary: DNA methylation, an important epigenetic mark regulating gene expression, plays a crucial role in various biological processes. MethBank 4.0 serves as a fundamental resource for the global research community, providing a wide range of services for integrating, archiving, analyzing, and visualizing DNA methylation data.
NUCLEIC ACIDS RESEARCH
(2023)
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
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Johanna M. Schafer, Xingyu Chen, Tong Xiao, Timothy D. Gauntner, Zihai Li, Dan Theodorescu
Summary: Loss of the Y chromosome (LOY) correlates with poor prognoses in bladder cancer patients. LOY mutations alter T cell function, promoting T cell exhaustion and sensitizing them to PD-1-targeted immunotherapy.
Article
Cell Biology
Florus C. de Jong, Teemu D. Laajala, Robert F. Hoedemaeker, Kimberley R. Jordan, Angelique C. J. van der Made, Egbert R. Boeve, Deric K. E. van der Schoot, Bart Nieuwkamer, Emiel A. M. Janssen, Tokameh Mahmoudi, Joost L. Boormans, Dan Theodorescu, James C. Costello, Tahlita C. M. Zuiverloon
Summary: The recommended treatment for high-risk non-muscle-invasive bladder cancer patients is tumor resection followed by adjuvant Bacillus Calmette-Guerin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. Identifying tumors unlikely to respond to BCG can lead to alternative treatments for these patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Peris R. Castaneda, Dan Theodorescu, Charles J. Rosser, Michael Ahdoot
Summary: Bladder cancer is a complex disease with variable prognosis, and recent studies have identified frequent genetic alterations and molecular subtypes. Personalized treatment strategies and the development of biomarkers to predict response and guide therapy in bladder cancer have become a focus of research. In this review, we summarize the latest studies on novel biomarkers in bladder cancer, specifically those intended to improve risk stratification and treatment selection, based on a search of recently published PubMed articles using relevant keywords.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Nina Rao, Gabriel J. Starrett, Mary L. Piaskowski, Kelly E. Butler, Yelena Golubeva, Wusheng Yan, Scott M. Lawrence, Michael Dean, Montserrat Garcia-Closas, Dalsu Baris, Alison Johnson, Molly Schwenn, Nuria Malats, Francisco X. Real, Manolis Kogevinas, Nathaniel Rothman, Debra T. Silverman, Lars Dyrskjot, Christopher B. Buck, Stella Koutros, Ludmila Prokunina-Olsson
Summary: Tobacco smoking is likely to cause a common mutation in bladder tumors, while viral infections may contribute to other mutations. Understanding the causes of these mutations could lead to new prevention and treatment strategies.
CANCER PREVENTION RESEARCH
(2023)
Article
Urology & Nephrology
Thomas W. Flaig, Catherine M. Tangen, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, David James McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared S. Fowles, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson Jr, Seth P. Lerner
Summary: This article mainly evaluated the predictive role of the COXEN gene expression model in neoadjuvant chemotherapy for bladder cancer, and conducted a secondary analysis of the association between COXEN scores and event-free survival and overall survival.
Article
Biotechnology & Applied Microbiology
Shan Wang, Shang Wang, Tongyu Hao, Shimao Zhu, Xinying Qiu, Yuqing Li, Xiaoxu Yang, Song Wu
Summary: In this study, a highly sensitive and quick method for Salmonella infection and drug resistance mutation detection was established using PCR and CRISPR-lbCas12a system. The method showed high sensitivity and specificity with clinical samples and detected a consistent mutant strain with DNA sequencing.
Review
Medicine, General & Internal
Lars Dyrskjot, Donna E. Hansel, Jason A. Efstathiou, Margaret A. Knowles, Matthew D. Galsky, Jeremy Teoh, Dan Theodorescu
Summary: Bladder cancer is a global health issue with distinct molecular subtypes and pathogenic pathways. Early detection and diagnosis are crucial for improving patient outcomes. Treatment options vary depending on the invasion level and include surgery and immunotherapy. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Infectious Diseases
Xuejiao Liao, Yuan Guan, Tetsuya Asakawa, Zixun Lin, Qingrong Tang, Zhenghua Ma, Shuting Wu, Xiaobin Wang, Jingke Dong, Liping Zhang, Jiayu Deng, Zhonghui Liao, Sumei Yang, Cheng Wang, Shuo Song, Hongyang Yi, Song Wu, Hongzhou Lu
Summary: The purpose of this study was to review clinical data and formulate recommendations for using saline as a rinse to reduce re-positive COVID-19 cases. The results showed that nasal douche treatment can shorten the time for virus nucleic acid to turn negative, thereby reducing the occurrence of re-positive cases.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Saravana Kumar Kailasam Mani, Wesley Huang, I. I. I. Kenneth H. Gouin, Yuzhou Chang, Tong Xiao, Qin Ma, Zihai Li, Simon R. V. Knott, Dan Theodorescu
Summary: In this study, single-cell RNA sequencing was used to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. Proportional and gene expression differences were found in epithelial and non-epithelial subpopulations between male and female tumors. Several genes were found to predict sex-specific survival in human BLCA datasets. Novel and clinically relevant sex-specific transcriptional signatures were identified, including immune cells in the tumor microenvironment. It validated the relevance of the BBN model for studying sex differences in human BLCA.
Review
Immunology
Jianxiong Zheng, Lei Peng, Shaohua Zhang, Haiyang Liao, Jiayao Hao, Song Wu, Haili Shen
Summary: This meta-analysis indicates that the systemic immune-inflammation index (SII) can serve as a valuable prognostic tool in patients with urothelial carcinoma (UC).
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Urology & Nephrology
Jun Gong, Daniel M. Kim, Michael R. Freeman, Hyung Kim, Leigh Ellis, Bethany Smith, Dan Theodorescu, Edwin Posadas, Robert Figlin, Neil Bhowmick, Stephen J. Freedland
Summary: Black men with prostate cancer have biologically distinct cancers compared to white men, including genetic alterations, protein differences, and tumor microenvironment. Socioeconomic status partially explains the disparities, but not completely. Further research on these biological differences can guide efforts to improve treatment outcomes for Black men.
NATURE REVIEWS UROLOGY
(2023)