Review
Oncology
Zeyuan Zheng, Jinxin Li, Yankuo Liu, Zhiyuan Shi, Zuodong Xuan, Kunao Yang, Chunlan Xu, Yang Bai, Meiling Fu, Qiaohong Xiao, Huimin Sun, Chen Shao
Summary: This review summarizes the mechanisms and biological behaviors of AR-V7 in enzalutamide resistance of castration-resistant prostate cancer (CRPC), providing novel insights for CRPC therapy.
Article
Biochemistry & Molecular Biology
Eunjeong Seo, Byula Jee, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Minyong Kang
Summary: In this study, the researchers discovered that the AR-V7/YAP1/TAZ axis represses the expression of SLC22A3, leading to resistance to enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC). This finding provides new insights into potential treatment targets for prostate cancer.
Article
Oncology
Lin Gao, Wenbo Zhang, Jing Zhang, Junmei Liu, Feifei Sun, Hui Liu, Jing Hu, Xin Wang, Xueli Wang, Peng Su, Shouzhen Chen, Sifeng Qu, Benkang Shi, Xueting Xiong, Weiwen Chen, Xuesen Dong, Bo Han
Summary: The study reveals that KIF15 contributes to enzalutamide resistance by enhancing AR signaling, and suggests that cotargeting KIF15 and AR may be an effective therapeutic strategy for prostate cancer.
Article
Cell Biology
Yuan Liu, Cuifu Yu, Zhenlong Shao, Xiaohong Xia, Tumei Hu, Weiyao Kong, Xiaoyue He, Wenshuang Sun, Yuanfei Deng, Yuning Liao, Hongbiao Huang
Summary: AR-V7, a crucial factor in driving CRPC, can be effectively degraded by nobiletin through inducing G0/G1 phase arrest and enhancing sensitivity of cells to enzalutamide, offering a novel approach for treating CRPC.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Neele Wuestmann, Konstantin Seitzer, Verena Humberg, Julia Vieler, Norbert Grundmann, Julie Steinestel, Dorothee Tiedje, Stefan Duensing, Laura-Maria Krabbe, Martin Boegemann, Andres Jan Schrader, Christof Bernemann, Katrin Schlack
Summary: This study found that the level of AR-FL and the appearance and increase of AR-Vs are associated with elevated levels of AR pre-mRNA in prostate cancer cells. The levels of AR-FL and AR-Vs also increase during disease progression. In patients undergoing ARTA treatment, AR-FL shows prognostic value but not predictive value. Additionally, even AR-V positive patients show a significant clinical response to ARTA treatment. Therefore, AR-FL and AR-V may be considered as prognostic biomarkers in mCRPC patients, but not predictive biomarkers.
BIOMARKER RESEARCH
(2023)
Article
Cell Biology
Haojie Chen, Jia Luo, Shaojun Chen, Bowen Shi, Xiaocui Zheng, Haiying Ji, Xiaoqian Zhang, Yujia Yin, Kun Du, Jie Ding, Yongjiang Yu
Summary: ABCC5 may serve as a novel target for enzalutamide-resistant CRPC treatment by affecting resistance to enzalutamide through its non-drug efflux function.
CELL DEATH DISCOVERY
(2022)
Article
Multidisciplinary Sciences
Manjul Rana, Jianrong Dong, Matthew J. Robertson, Cristian Coarfa, Nancy L. Weigel
Summary: This study found differences in transcription and splicing regulation between AR-V7 and AR in prostate cancer, leading to the generation of different gene products.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Balaji Chandrasekaran, Subhasish Tapadar, Bocheng Wu, Uttara Saran, Ashish Tyagi, Alexis Johnston, David A. Gaul, Adegboyega K. Oyelere, Chendil Damodaran
Summary: SBI-46, an antiandrogen and histone deacetylase inhibitor, demonstrates anticancer effects on castration-resistant prostate cancer (CRPC) by downregulating the expression of AR and AR-splice variants. It induces apoptosis by activating pro-apoptotic genes and inhibiting anti-apoptotic genes. Additionally, oral administration of SBI-46 suppresses the growth of CRPC xenograft tumors expressing AR or both AR and AR-SV.
Article
Oncology
Masahiro Sugiura, Hiroaki Sato, Atsushi Okabe, Masaki Fukuyo, Yasunobu Mano, Ken-ichi Shinohara, Bahityar Rahmutulla, Kosuke Higuchi, Maihulan Maimaiti, Manato Kanesaka, Yusuke Imamura, Tomomi Furihata, Shinichi Sakamoto, Akira Komiya, Naohiko Anzai, Yoshikatsu Kanai, Jun Luo, Tomohiko Ichikawa, Atsushi Kaneda
Summary: The study found that AR-V7 contributes to the proliferation of CRPC by activating both common AR/AR-V7 target genes and specific AR-V7 target genes, such as NUP210 and SLC3A2. These findings suggest that targeting NUP210 and SLC3A2 may be a potential therapeutic strategy for CRPC.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Khrystany T. Isebia, Martijn P. Lolkema, Guido Jenster, Ronald de Wit, John W. M. Martens, Job van Riet
Summary: This study found that in metastatic castration-resistant prostate cancer, in addition to AR-V7, AR45 and AR-V3 were also commonly seen AR splice variants. The presence of any AR-Vs may be associated with higher AR expression. These AR-Vs could potentially serve as predictive and prognostic biomarkers in metastatic castration-resistant prostate cancer, similar or complementary to AR-V7.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Boya Zhang, Mingpeng Zhang, Chunyi Shen, Guancong Liu, Fan Zhang, Jingyu Hou, Weitao Yao
Summary: The study revealed the key role of LncRNA PCBP1-AS1 in drug resistance of castration-resistant prostate cancer, by stabilizing the AR/AR-V7 complex to prevent degradation. Targeting PCBP1-AS1 can significantly restore drug sensitivity in resistant tumors.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Adam G. Sowalsky, Ines Figueiredo, Rosina T. Lis, Ilsa Coleman, Bora Gurel, Denisa Bogdan, Wei Yuan, Joshua W. Russo, John R. Bright, Nichelle C. Whitlock, Shana Y. Trostel, Anson T. Ku, Radhika A. Patel, Lawrence D. True, Jonathan Welti, Juan M. Jimenez-Vacas, Daniel Nava Rodrigues, Ruth Riisnaes, Antje Neeb, Cynthia T. Sprenger, Amanda Swain, Scott Wilkinson, Fatima Karzai, William L. Dahut, Steven P. Balk, Eva Corey, Peter S. Nelson, Michael C. Haffner, Stephen R. Plymate, Johann S. de Bono, Adam Sharp
Summary: This study demonstrates that further analytical validation and clinical qualification are required before AR-V7 can be considered for clinical use in CSPC as a predictive biomarker.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Mirielle C. Nauman, Jong Hoon Won, Sakina M. Petiwala, Bhaskar Vemu, Hyun Lee, Maria Sverdlov, Jeremy J. Johnson
Summary: A major limitation of current prostate cancer pharmacotherapy is the inability to target androgen receptor variants or mutants. This study evaluated the novel ability of a-mangostin to degrade androgen receptor and its variants. Prostate cancer cells treated with a-mangostin showed decreased levels of both wild-type and mutated androgen receptors. In addition, the study suggests a new therapeutic approach for prostate cancer through the degradation of androgen receptor with the assistance of BiP, an ER chaperone protein.
Review
Biochemistry & Molecular Biology
Navid Sobhani, Praveen Kumar Neeli, Alberto D'Angelo, Matteo Pittacolo, Marianna Sirico, Ilaria Camilla Galli, Giandomenico Roviello, Gabriella Nesi
Summary: Metastatic prostate cancer is the most common cancer in males with a poor prognosis, and many patients develop the AR-V7 variant. AR-V7 acts as a transcription factor in the nucleus, repressing crucial tumor suppressor genes. Anti-AR-V7 drugs show promise for this subset of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Jing Wei, Lijuan Yin, Jingjing Li, Jing Wang, Tianjie Pu, Peng Duan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: The study reveals a reciprocal regulatory circuit between MAOA and AR in prostate cancer, with implications for cancer development and growth, particularly CRPC. Targeting MAOA may enhance the efficacy of AR-targeted therapies.
Review
Pharmacology & Pharmacy
Maria Teresa Borrello, Derek Mann
Summary: Chronic liver diseases lack effective pharmacological therapies and fibrosis, a major precursor of liver cirrhosis, is the focus of our research group. Fibrosis is a progressive disturbance of liver sinusoidal architecture caused by connective tissue deposition. Understanding the multifactorial events and various cell types involved in fibrosis initiation and progression is crucial. Developing experimental models of liver fibrosis and identifying critical factors that lead to cirrhosis will aid in the development of more effective therapies. This review provides an overview of hepatic fibrosis processes and therapeutic approaches based on a deep understanding of molecular regulation of fibrogenesis in the liver.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Rachael Arthur, Alexander Wathen, A. Elizabeth Lemm, K. Freda Stevenson, Francesco Forconi, J. Adam Linley, J. Andrew Steele, Graham Packham, Beatriz Valle-Argos
Summary: BTK inhibitors (BTKi) have shown significant improvement in the treatment of chronic lymphocytic leukemia (CLL) and certain forms of B-cell lymphoma. However, the activation of BTK-independent calcium signaling may limit the efficacy of BTKi. Inhibition of SYK or dual inhibition of BTK and RAC may be alternative strategies to enhance pathway blockade.
CELLULAR SIGNALLING
(2022)
Article
Immunology
Denise S. M. Boulanger, Leon R. Douglas, Patrick J. Duriez, Yoyel Kang, Neil Dalchau, Edd James, Tim Elliott
Summary: Tapasin, a component of MHC I peptide loading complex, plays a key role in shaping the hierarchy of CD8+ T-cell responses to tumors and pathogens by editing the repertoire of peptides presented at the cell surface. The level of tapasin expression affects peptide off-rate and abundance, and each peptide has a unique tapasin bonus fingerprint. Optimal tapasin expression level varies for each peptide in the immunopeptidome, depending on its off-rate and abundance. This finding is important in understanding immune responses and immune escape.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Matteo Santoni, Zin W. Myint, Thomas Buettner, Hideki Takeshita, Yohei Okada, Elaine T. Lam, Danielle Gilbert, Zsofia Kueronya, Deniz Tural, Renate Pichler, Enrique Grande, Simon J. Crabb, Robert Kemp, Francesco Massari, Sarah Scagliarini, Roberto Iacovelli, Nuno Vau, Umberto Basso, Marco Maruzzo, Javier Molina-Cerrillo, Luca Galli, Aristotelis Bamias, Ugo De Giorgi, Paolo Andrea Zucali, Mimma Rizzo, Emmanuel Seront, Lazar Popovic, Orazio Caffo, Sebastiano Buti, Ravindran Kanesvaran, Jindrich Kopecky, Jakub Kucharz, Annalisa Zeppellini, Ondrej Fiala, Johannes Landmesser, Jawaher Ansari, Patrizia Giannatempo, Alessandro Rizzo, Ignacio Ortego Zabalza, Fernando Sabino M. Monteiro, Nicola Battelli, Fabio Calabro, Camillo Porta
Summary: This study investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC, and confirmed its role in treating patients who are unfit for cisplatin therapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Dean Bryant, Lindsay Smith, Karly Rai Rogers-Broadway, Laura Karydis, Jeongmin Woo, Matthew D. Blunt, Francesco Forconi, Freda K. Stevenson, Christopher Goodnow, Amanda Russell, Peter Humburg, Graham Packham, Andrew J. Steele, Jonathan C. Strefford
Summary: Chronic lymphocytic leukaemia (CLL) cells can express unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain (IGHV) genes, with differences in clinical behaviors, B cell receptor (BCR) signaling capacity, and transcriptional profiles. Through mRNA/miRNA sequencing of 38 CLL cases, researchers identified differentially expressed mRNAs and miRNAs between U-CLL and M-CLL, as well as potential regulatory roles of the 14q32 miRNA locus in CLL-related gene regulation and BCR signaling.
Correction
Biochemistry & Molecular Biology
Thomas Powles, Mark Kockx, Alejo Rodriguez-Vida, Ignacio Duran, Simon J. Crabb, Michiel S. van der Heijden, Bernadett Szabados, Albert Font Pous, Gwenaelle Gravis, Urbano Anido Herranz, Andrew Protheroe, Alain Ravaud, Denis Maillet, Maria Jose Mendez, Cristina Suarez, Mark Linch, Aaron Prendergast, Pieter-Jan van Dam, Diana Stanoeva, Sofie Daelemans, Sanjeev Mariathasan, Joy S. Tea, Kelly Mousa, Romain Banchereau, Daniel Castellano
Article
Oncology
Simon Crabb, Robin Wickens, Sarah Jane-Bibby, Denise Dunkley, Megan Lawrence, Allen Knight, Robert Jones, Alison Birtle, Robert Huddart, Mark Linch, Jonathan Martin, Adam Coleman, Konstantinos Boukas, Hannah Markham, Gareth Griffiths
Summary: This study aims to evaluate the safety and efficacy of PD-L1 directed immunotherapy atezolizumab in UTSCC patients. Preliminary translational data suggests potential therapeutic value. Through this study, we hope to provide a new treatment option for UTSCC patients.
Article
Oncology
Ondrej Fiala, Sebastiano Buti, Hideki Takeshita, Yohei Okada, Francesco Massari, Georgia Anguera Palacios, Michele Dionese, Sarah Scagliarini, Thomas Buettner, Giuseppe Fornarini, Zin W. Myint, Luca Galli, Vinicius Carrera Souza, Renate Pichler, Ugo De Giorgi, Maria Natalia Gandur Quiroga, Danielle Gilbert, Lazar Popovic, Enrique Grande, Giulia Mammone, Rossana Berardi, Simon J. Crabb, Javier Molina-Cerrillo, Marcelo Freitas, Murilo Luz, Roberto Iacovelli, Fabio Calabro, Deniz Tural, Francesco Atzori, Zsofia Kueronya, Rita Chiari, Saul Campos, Orazio Caffo, Andre P. Fay, Jakub Kucharz, Paolo Andrea Zucali, Jose Augusto Rinck, Annalisa Zeppellini, Diogo Assed Bastos, Gaetano Aurilio, Augusto Mota, Karine Trindade, Cinzia Ortega, Juan Pablo Sade, Mimma Rizzo, Nuno Vau, Patrizia Giannatempo, Allan Barillas, Fernando Sabino Marques Monteiro, Breno Dauster, Carlo Cattrini, Lucas Nogueira, Roni de Carvalho Fernandes, Emmanuel Seront, Luis Garcia Aceituno, Francesco Grillone, Hernan Javier Cutuli, Mauricio Fernandez, Maria Bassanelli, Giandomenico Roviello, Halima Abahssain, Giuseppe Procopio, Michele Milella, Jindrich Kopecky, Angelo Martignetti, Carlo Messina, Manuel Caitano, Eva Inman, Ravindran Kanesvaran, Daniel Herchenhorn, Daniele Santini, Ray Manneh, Renato Bisonni, Roubini Zakopoulou, Alessandra Mosca, Franco Morelli, Fernando Maluf, Andrey Soares, Fernando Nunes, Alvaro Pinto, Anca Zgura, Lorena Incorvaia, Jawaher Ansari, Ignacio Ortego Zabalza, Johannes Landmesser, Alessandro Rizzo, Veronica Mollica, Giulia Sorgentoni, Nicola Battelli, Camillo Porta, Joaquim Bellmunt, Matteo Santoni
Summary: This study found that concomitant use of proton pump inhibitors (PPI) had a negative impact on the overall survival and progression-free survival of patients with metastatic urothelial cancer (mUC) receiving pembrolizumab treatment in a real-world setting. However, the use of statins or metformin did not affect treatment response or survival.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Simone Critchlow, Ash Bullement, Simon Crabb, Robert Jones, Katerina Christoforou, Amerah Amin, Ying Xiao, Venediktos Kapetanakis, Agnes Benedict, Jane Chang, Mairead Kearney, Anthony Eccleston
Summary: This study assessed the cost-effectiveness of Avelumab as first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma in Scotland. The costs and treatment benefits of Avelumab were estimated using data from a clinical trial, national databases, published literature, and expert opinions. The results suggest that Avelumab is a cost-effective treatment option for these patients in Scotland.
Article
Medicine, Research & Experimental
Simon Crabb, Alannah Morgan, Myra S. S. Hunter, Evgenia Stefanopoulou, Gareth Griffiths, Alison Richardson, Deborah Fenlon, Louisa Fleure, James Raftery, Cherish Boxall, Sam Wilding, Jacqueline Nuttall, Zina Eminton, Emma Tilt, Alice O'Neill, Roger Bacon, Jonathan Martin
Summary: This study aims to assess the effectiveness of a guided self-help cognitive behavioural therapy (CBT) intervention, delivered by the existing NHS prostate cancer CNS team, in reducing the impact of hot flushes and night sweats (HFNS) in men undergoing androgen deprivation therapy (ADT). It will evaluate the intervention through a randomized controlled trial and explore the key influencers to its implementation through a process evaluation.
Article
Immunology
Osman Dadas, Joel D. Allen, Sarah L. Buchan, Jinny Kim, H. T. Claude Chan, C. Ian Mockridge, Patrick J. Duriez, Anne Rogel, Max Crispin, Aymen Al-Shamkhani
Summary: This study investigates the generation and activity of soluble variants of CD70 and compares their efficacy with an agonist anti-CD27 antibody. The results show that dtCD70-Fc, a dimer-of-trimer protein, can enhance T cell proliferation in vitro, but is less effective than anti-CD27 antibody in boosting a CD8 T cell vaccine response in vivo. However, reducing the glycosylation of dtCD70-Fc improves its half-life and T cell stimulatory activity. Additionally, FcγR binding is found to be important for the maximal boosting of a CD8 T cell response by dtCD70-Fc.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Anna Claudia Silva, Daniel Clemente de Moraes, Denilson Costa do Carmo, Giselle Cristina Casaes Gomes, A. Ganesan, Rosangela Sabbatini Capella Lopes, Antonio Ferreira-Pereira, Claudio Cerqueira Lopes
Summary: Azoles are the main antifungal drugs used to treat invasive candidiasis, but their efficacy is limited by fungal resistance mechanisms like overexpression of efflux pumps. A potential strategy to overcome this resistance is to inhibit the efflux process. This study aimed to synthesize altissimacoumarin D and its analogues to evaluate their ability to reverse the resistance phenotype of Candida albicans.
Review
Urology & Nephrology
Megan Giles, Simon J. Crabb
Summary: Muscle-invasive bladder cancer is difficult to treat, with poor prognosis and high relapse rates. Platinum-based combination chemotherapy is a commonly used systemic treatment option, but it only provides modest improvements in cure rates. PD-1/PDL1 checkpoint-directed immunotherapy shows some promise in advanced disease. Adjuvant immunotherapy has contradictory results, and the development of accurate predictive biomarkers is crucial for future treatment options.
RESEARCH AND REPORTS IN UROLOGY
(2023)
Article
Oncology
Ondrej Fiala, Sebastiano Buti, Hideki Takeshita, Yohei Okada, Francesco Massari, Georgia Anguera Palacios, Michele Dionese, Sarah Scagliarini, Thomas Buettner, Giuseppe Fornarini, Zin W. Myint, Luca Galli, Vinicius Carrera Souza, Renate Pichler, Ugo De Giorgi, Maria Natalia Gandur Quiroga, Danielle Gilbert, Lazar Popovic, Enrique Grande, Giulia Mammone, Rossana Berardi, Simon J. Crabb, Javier Molina-Cerrillo, Marcelo Freitas, Murilo Luz, Roberto Iacovelli, Fabio Calabro, Deniz Tural, Francesco Atzori, Zsofia Kuronya, Rita Chiari, Saul Campos, Orazio Caffo, Andre P. Fay, Jakub Kucharz, Paolo Andrea Zucali, Jose Augusto Rinck, Annalisa Zeppellini, Diogo Assed Bastos, Gaetano Aurilio, Augusto Mota, Karine Trindade, Cinzia Ortega, Juan Pablo Sade, Mimma Rizzo, Nuno Vau, Patrizia Giannatempo, Allan Barillas, Fernando Sabino Marques Monteiro, Breno Dauster, Carlo Cattrini, Lucas Nogueira, Roni de Carvalho Fernandes, Emmanuel Seront, Luis Garcia Aceituno, Francesco Grillone, Hernan Javier Cutuli, Mauricio Fernandez, Maria Bassanelli, Giandomenico Roviello, Halima Abahssain, Giuseppe Procopio, Michele Milella, Jindrich Kopecky, Angelo Martignetti, Carlo Messina, Manuel Caitano, Eva Inman, Ravindran Kanesvaran, Daniel Herchenhorn, Daniele Santini, Ray Manneh, Renato Bisonni, Roubini Zakopoulou, Alessandra Mosca, Franco Morelli, Fernando Maluf, Andrey Soares, Fernando Nunes, Alvaro Pinto, Anca Zgura, Lorena Incorvaia, Jawaher Ansari, Ignacio Ortego Zabalza, Johannes Landmesser, Alessandro Rizzo, Veronica Mollica, Giulia Sorgentoni, Nicola Battelli, Camillo Porta, Joaquim Bellmunt, Matteo Santoni
Summary: This sub-analysis of a real-world study aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on the outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. The study found that concomitant PPI use was associated with inferior progression-free survival (PFS) and overall survival (OS), while the use of statins or metformin was not associated with response or survival.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Chemistry, Organic
Paulo Eliandro da Silva Junior, Shaiani Maria Gil de Melo, Murilo Helder de Paula, Ricardo Vessecchi, Till Opatz, James E. H. Day, A. Ganesan, Flavio da Silva Emery
Summary: This article discusses the reactivity of 6-azaindazole and 2,6-naphthyridine, which are important in fragment-based drug discovery. The article introduces selective functionalization methods for pyridone and pyrazole, as well as a new method for selective functionalization of heterocycle 1.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)