Article
Medicine, General & Internal
Min Ho An, Min Seo Kim, Chungsoo Kim, Tae Il Noh, Kwan Joong Joo, Dong Hun Lee, Kyu-Ho Yi, Jeong Woo Kwak, Tae-Ho Hwang, Rae Woong Park, Seok Ho Kang
Summary: This study analyzed data from male patients and found that the use of 5-alpha-reductase inhibitors (5-ARI) was associated with a lower risk of mortality, bladder instillation, and radical cystectomy in patients prior to the diagnosis of bladder cancer. The study suggests that the use of 5-ARI may reduce the risk of bladder cancer progression.
Article
Cell Biology
Wei Song, Ke Yang, Jianjun Luo, Zhiyong Gao, Yunliang Gao
Summary: N6-methyladenosine is a crucial RNA modification that plays a key role in bladder cancer development, and the mechanism involves the regulation of PYCR1 expression by fat-mass and obesity-associated protein (FTO) through its demethylase activity. Our study highlights the UPS18/FTO/PYCR1 signaling network as potential therapeutic targets for bladder cancer.
Article
Oncology
Jianfeng Yang, Jin Xu, Qian Gao, Fan Wu, Wei Han, Chao Yu, Youyang Shi, Yunhua Qiu, Yuanbiao Chen, Xiqiu Zhou
Summary: This study revealed that increased expression of ADCY2 was significantly correlated with increased tumor heterogeneity, predicting worse survival and immunotherapy response in BCa patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Bing Lu, Jiatian Wei, Houhong Zhou, Jie Chen, Yuqing Li, Liefu Ye, Wei Zhao, Song Wu
Summary: Epigenetic dysregulation plays a role in bladder cancer. KDM2A, an important epigenetic regulator, is found to be upregulated in bladder cancer due to gene copy number gain and a super-enhancer. Knockdown of KDM2A suppresses the growth and invasion of bladder cancer cells and inhibits tumor growth. KDM2A suppresses RARRES3 expression through demethylation and the KDM2A/RARRES3 axis may be a promising therapeutic target for high-grade bladder cancer.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Huimin Xu, Lingao Ju, Yaoyi Xiong, Mengxue Yu, Fenfang Zhou, Kaiyu Qian, Gang Wang, Yu Xiao, Xinghuan Wang
Summary: RNF126 is highly expressed in various cancers and acts as an oncogene in bladder cancer by promoting cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway. It directly interacts with and regulates the stability of PTEN, an inhibitor of the PI3K/AKT pathway, through poly-ubiquitination. Knockdown of PTEN restores the effects of RNF126 silencing on cell proliferation, metastasis, and tumor formation in bladder cancer cells.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Shumei Zhang, Jingyu Zhang, Qichao Zhang, Yingjian Liang, Youwen Du, Guohua Wang
Summary: The study suggests that DNA methylation is associated with the occurrence of bladder cancer, and genes with differential DNA methylation levels can serve as potential biomarkers for the cancer. FASLG and PRKCZ have been identified as prognostic biomarkers for bladder cancer through Cox proportional hazard regression analysis. Patients can be categorized into high or low risk groups based on this two-gene prognostic model, which can help evaluate patient survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Tianyuan Liu, Xuan Zhao, Yuan Lin, Qi Luo, Shaosen Zhang, Yiyi Xi, Yamei Chen, Lin Lin, Wenyi Fan, Jie Yang, Yuling Ma, Alok K. Maity, Yanyi Huang, Jianbin Wang, Jiang Chang, Dongxin Lin, Andrew E. Teschendorff, Chen Wu
Summary: This study develops a computational strategy to identify stem-like preneoplastic cells that may drive cancer progression by dissecting the heterogeneity of differentiation states within a preneoplastic cell population.
Review
Oncology
Yuhao Zhao, Mao Yang, Shijia Wang, Sk Jahir Abbas, Junzhe Zhang, Yongsheng Li, Rong Shao, Yingbin Liu
Summary: This review focuses on the mechanistic insights of DNA, histone, and RNA methylation in regulating the progression of pancreatic cancer. The roles of methylation regulators in modulating gene expression associated with cell proliferation, invasion, and apoptosis are discussed. Recent clinical trials on methylation drug targeting are also explored. Understanding the novel regulatory mechanisms of methylation modification may offer alternative opportunities to improve therapeutic efficacy in combating this devastating disease.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Shiv Verma, Eswar Shankar, Spencer Lin, Vaibhav Singh, E. Ricky Chan, Shufen Cao, Pingfu Fu, Gregory T. MacLennan, Lee E. Ponsky, Sanjay Gupta
Summary: This study identified a 3-gene signature panel with prognostic value in bladder cancer, including CDKN2A, CDC20, CTSV, FOXM1, MAGEA6, KRT23, and S100A9. These genes were confirmed to have strong prognostic values in bladder cancer and were validated through qRT-PCR in various human bladder cancer cells representing stage-specific disease progression. Additionally, ULCAN, human protein atlas, and The Cancer Genome Atlas datasets were used to confirm the predictive value of these genes in bladder cancer progression.
Article
Cell Biology
Ganping Wang, Yarong Dai, Kang Li, Maosheng Cheng, Gan Xiong, Xiaochen Wang, Shuang Chen, Zhi Chen, Jianwen Chen, Xiuyun Xu, Rong-song Ling, Liang Peng, Demeng Chen
Summary: The study demonstrates that Mettl3-mediated m(6)A modification is crucial for the activation of TEK-VEGF-A-mediated tumor progression and angiogenesis in bladder cancer. Experimental results using transgenic mouse models and bladder cancer stem cell populations showed that depletion of Mettl3 inhibits tumor oncogenesis and progression in bladder cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Yuqi Xia, Weimin Yu, Fan Cheng, Ting Rao, Yuan Ruan, Run Yuan, Jinzhuo Ning, Xiangjun Zhou, Fangyou Lin, Di Zheng
Summary: Blue laser irradiation inhibits bladder cancer proliferation in a density-dependent manner, suppresses migration, invasion, and the EMT process in T24 and EJ cell lines, possibly mediated via suppression of the MAPK/MEK/ERK pathway. The use of low-energy blue laser may have a safe and anti-tumor effect in the diagnosis and treatment of bladder cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Tae Jeong Oh, Eunkyung Lim, Bo-Ram Bang, Justin Junguek Lee, Yong Gil Na, Ju Hyun Shin, Jae Sung Lim, Ki Hak Song, Sungwhan An
Summary: In this study, DNA methylation analysis identified potential biomarkers for early detection of bladder cancer (BCa) for use in urine-based tests. The detection of PENK methylation in urine showed high accuracy and sensitivity, making it a noninvasive method for BCa diagnosis.
Article
Medicine, Research & Experimental
Katerina-Marina Pilala, Maria-Alexandra Papadimitriou, Konstantina Panoutsopoulou, Petros Barbarigos, Panagiotis Levis, Georgios Kotronopoulos, Konstantinos Stravodimos, Andreas Scorilas, Margaritis Avgeris
Summary: Bladder cancer (BlCa) is characterized by heterogeneous molecular landscape and lacks personalized treatment. In this study, we investigated the epigenetic regulation of the miR-143/145 cluster in BlCa. We found that the methylation of MIR145 core promoter was associated with disease progression and poor survival in BlCa patients. Combining MIR145 core promoter methylation with established disease markers improved risk stratification and prediction of treatment outcome. Our findings highlight the importance of personalized risk stratification and management in BlCa.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Oncology
Shuangjie Liu, Zhuonan Liu, Chiyuan Piao, Zhe Zhang, Chuize Kong, Lei Yin, Xi Liu
Summary: The study reveals PRMT5 as a therapeutic target for bladder cancer and identifies FKA, extracted from the kava plant, as an inhibitor of PRMT5 for the treatment of bladder cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Nataly W. El-Haddad, Michelle El Kawak, Khalil El Asmar, Michel E. Jabbour, Mohamad A. Moussa, Rima R. Habib, Hassan R. Dhaini
Summary: The study found that AhRR demethylation in bladder cancer tissue was associated with muscle-invasive tumors and FGFR3 gene mutations, but did not predict smoking status.
Article
Oncology
Alejo Rodriguez-Vida, Pablo Maroto, Albert Font, Cristina Martin, Begona Mellado, Alex Corbera, Mayra Orrillo, Oscar Reig, Rosa Querol, Alejandro Rios-Hoyo, Laia Cano, Judith Alonso, Gemma Martinez, Susana Galtes, Alvaro Taus, Maria Martinez-Garcia, Nuria Juanpere, Oscar Juan, Joaquim Bellmunt
Summary: This study investigated the safety and efficacy of avelumab plus carboplatin in mCRPC patients. Despite the significant treatment-related adverse events, this therapy was associated with a prolonged overall survival in heavily pretreated patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Cora N. Sternberg, Daniel P. Petrylak, Joaquim Bellmunt, Hiroyuki Nishiyama, Andrea Necchi, Howard Gurney, Jae-Lyun Lee, Michiel S. van der Heijden, Eli Rosenbaum, Nicolas Penel, See-Tong Pang, Jian-Ri Li, Xavier Garcia del Muro, Florence Joly, Zsuzsanna Papai, Weichao Bao, Peter Ellinghaus, Chengxing Lu, Mitchell Sierecki, Sabine Coppieters, Keiko Nakajima, Tatiane Cristine Ishida, David Quinn
Summary: The purpose of this study was to assess the efficacy and safety of rogaratinib compared to chemotherapy in patients with FGFR-positive advanced/metastatic UC. The results showed comparable overall survival and response rates between rogaratinib and chemotherapy, with manageable side effects. Exploratory analysis suggested that FGFR3 gene alterations may be better predictors of rogaratinib response in FGFR-altered UC patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleix Noguera-Castells, Carlos A. Garcia-Prieto, Damiana Alvarez-Errico, Manel Esteller
Summary: DNA methylation, a well-studied epigenetic mark, plays a critical role in gene regulation and is altered in cancer and other diseases. The newly developed 900K EPIC v2 microarray provides significant improvements in coverage and includes additional probes for DNA cis-regulatory regions. Validation studies demonstrate the reproducibility and versatility of this updated tool for studying the DNA methylome.
Article
Biochemistry & Molecular Biology
David Ortega-Alarcon, Rafael Claveria-Gimeno, Sonia Vega, Olga C. Jorge-Torres, Manel Esteller, Olga Abian, Adrian Velazquez-Campoy
Summary: Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark that interacts with MeCP2 in a distinct mode with a specific thermodynamic signature. Mutations associated with Rett syndrome alter the interaction between MeCP2 and dsDNA in a cytosine modification-specific manner, which may be correlated with disease onset time and clinical severity score.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Miriam Gene, Miriam Cuatrecasas, Irene Amat, Jesus Alberto Veiga, Maria Jesus Fernandez Acenero, Victoria Fuste Chimisana, Jordi Tarragona, Ismael Jurado, Rebeca Fernandez-Victoria, Carolina Martinez Ciarpaglini, Cristina Alenda Gonzalez, Carlos Zac, Pilar Ortega de la Obra, Maria Teresa Fernandez-Figueras, Manel Esteller, Eva Musulen
Summary: Colitis-associated colorectal carcinoma (CAC) in inflammatory bowel disease (IBD) is caused by p53 alterations and follows a chronic inflammation-dysplasia-cancer carcinogenesis pathway. Gastric metaplasia (GM) is described as the initial event of serrated colorectal cancer (CRC) in the colon mucosa under chronic stress. This study analyzed p53 alterations and microsatellite instability (MSI) to characterize CAC and investigate its relationship with GM. Results showed that p53 mutation pattern was present in more than half of the CAC cases, with stable (MSS) tumors being the most common and MUC5AC negative. Only six unstable (MSI-H) tumors had wild-type p53 pattern (p=0.010) and were MUC5AC positive (p=0.005). MUC5AC staining was more frequently observed in intestinal mucosa with inflammation or chronic changes than in CAC, particularly in those with wild-type p53 pattern and MSS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Thomas Powles, Se Hoon Park, Claudia Caserta, Begona P. Valderrama, Howard Gurney, Anders Ullen, Yohann Loriot, Srikala S. S. Sridhar, Cora N. N. Sternberg, Joaquim Bellmunt, Jeanny B. B. Aragon-Ching, Jing Wang, Bo Huang, Robert J. J. Laliberte, Alessandra di Pietro, Petros Grivas
Summary: Clinical trials often have multiple endpoints that mature at different times. Clinical Trial Updates provide the opportunity to disseminate additional results from studies for which the primary endpoint has already been reported.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Maxime Janin, Manel Esteller
Summary: Mutations in splicing factors are commonly found in CLL, but other mechanisms such as METTL3 overexpression can also lead to abnormal splicing. METTL3 deposits epitranscriptomic marks in spliceosome transcripts, causing aberrant splicing, but also vulnerability to METTL3 inhibitors.
BLOOD CANCER DISCOVERY
(2023)
Review
Oncology
Maxime Janin, Veronica Davalos, Manel Esteller
Summary: Most cancer-related deaths and illnesses can be attributed to metastasis. The role of epigenetic and epitranscriptomic changes in the origin and progression of cancer has been extensively demonstrated. These two-layer regulatory mechanisms, driven by DNA or RNA modifiers, are finely controlled in normal tissue but dysregulated in cancer. Understanding these mechanisms could have important clinical implications for prevention and management of advanced malignancies. Reversing these epi-alterations with small molecules or inhibitors against epi-modifiers could offer novel therapeutic alternatives.
CANCER AND METASTASIS REVIEWS
(2023)
Editorial Material
Urology & Nephrology
Chris Labaki, Eddy Saad, Toni K. Choueiri, Joaquim Bellmunt
Letter
Oncology
Carlos A. Garcia-Prieto, Veronica Davalos, Manel Esteller
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Lucia Salz, Alexander Seitz, Daniel Schaefer, Julia Franzen, Tatjana Holzer, Carlos A. Garcia-Prieto, Iris Buerger, Olaf Hardt, Manel Esteller, Wolfgang Wagner
Summary: CAR T cell expansion during culture leads to DNA hypermethylation, which downregulates the expression of genes relevant to T cell function. This hypermethylation signature can predict cell culture time and is associated with reduced long-term survival and therapeutic outcome in CAR T cell products.
Article
Oncology
Thomas Seisen, Muhieddine Labban, Stuart R. R. Lipsitz, Mark A. A. Preston, Matthew Mossanen, Joaquim Bellmunt, Morgan Roupret, Toni K. K. Choueiri, Adam S. S. Kibel, Maxine Sun, Quoc-Dien Trinh
Summary: This study examined the ecological association between tobacco smoking prevalence and bladder cancer incidence and found that the association was not significant. However, there was a significant association between tobacco smoking prevalence and lung cancer incidence.
Article
Pathology
Laura Segales, Nuria Juanpere, Nerea Gallarin, Marta Lorenzo, David Lopez, Julia Perera-Bel, Alejo Rodriguez-Vida, Lluis Fumado, Lluis Cecchini, Joaquim Bellmunt, Josep Lloreta-Trull, Silvia Hernandez-Llodra
Summary: The impact of tumor focality on prostate cancer prognosis has been investigated. The study found relevant and consistent molecular differences between unifocal and multifocal prostate cancer. An immunohistochemical panel may be useful in predicting the outcome of multifocal prostate cancer cases.
Review
Oncology
Rosa Nadal, Begona P. Valderrama, Joaquim Bellmunt
Summary: Despite recent advances, advanced-stage urothelial carcinoma (aUC) remains difficult to cure, but the availability of maintenance therapy with avelumab, an anti-PD-1 antibody, has improved the survival outcomes of patients. This review provides an overview of the treatment of aUC, including promising new therapeutic modalities and their potential impact on clinical outcomes.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Edilene Siqueira, Bo-Hyun Kim, Larry Reser, Robert Chow, Kerry Delaney, Manel Esteller, Mark M. Ross, Jeffrey Shabanowitz, Donald F. Hunt, Sonia Guil, Juan Ausio
Summary: This study used a neural cell line derived from the human ventral mesencephalon, called ReNCell, and its MeCP2 knock out to investigate the changes in linker histones during neural cell differentiation. The results showed that MeCP2 played a crucial role in dendrite and axon development and exhibited extensive co-localization with linker histones. Additionally, the size of the nucleus decreased during differentiation, but the MeCP2 knock out cells showed a significant increase in nucleus size after differentiation.