Article
Biochemistry & Molecular Biology
Bin Yang, Alicia C. Borgeaud, Marcela Buricova, Lorene Aeschbach, Oscar Rodriguez-Lima, Gustavo A. Ruiz Buendia, Cinzia Cinesi, Alysha S. Taylor, Tuncay Baubec, Vincent Dion
Summary: Studies show that HDAC5 and DNMT1 do not affect the instability of expanded CAG/CTG repeats, but the expanded repeats reduce the effectiveness of gene silencing mediated by HDAC5 and DNMT1.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Johanna Wolfsberger, Habib A. M. Sakil, Leilei Zhou, Niek van Bree, Elena Baldisseri, Sabrina de Souza Ferreira, Veronica Zubillaga, Marina Stantic, Nicolas Fritz, Johan Hartman, Charlotte Rolny, Margareta T. Wilhelm
Summary: Low levels of TAp73 are correlated with an increased NF-kappa B-regulated inflammatory signature in breast cancer, leading to hyperactivation of NF-kappa B pathway and secretion of Ccl2, which results in accumulation and phenotype transformation of pro-tumoral macrophages. These findings suggest that TAp73 regulates macrophage accumulation and phenotype in breast cancer through inhibition of the NF-kappa B pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Jiajie Tu, Yilong Fang, Dafei Han, Xuewen Tan, Zhen Xu, Haifeng Jiang, Xinming Wang, Wenming Hong, Wei Wei
Summary: This study explores the potential clinical value and molecular mechanisms of miRNA-22 in tumor cell phagocytosis by macrophages and more efficient T cell priming. miR-22 upregulation enhances the phagocytic ability of macrophages, inhibits glioma cell proliferation and migration, and promotes antigen presentation and efficient T cell priming. The study also identifies HDAC6 as a target and NF-kappa B signaling as a pathway associated with miR-22 in tumor-associated macrophages of glioma.
Article
Oncology
Jianhong Chen, Mark D. D. Long, Sirinapa Sribenja, Sung Jun Ma, Li Yan, Qiang Hu, Song Liu, Thaer Khoury, Chi-Chen Hong, Elisa Bandera, Anurag K. Singh, Elizabeth A. Repasky, Elizabeth G. Bouchard, Michael Higgins, Christine B. Ambrosone, Song Yao
Summary: In this study, the researchers analyzed the tumor DNA methylation data of 694 breast cancer patients and found that household income was associated with tumor DNA methylation, while educational attainment was not. The methylation levels of NNT and GPR37 genes were negatively correlated with household income, and these genes are involved in stress response and immune response. This correlation was consistent in both black and white patients. These findings suggest that socioeconomic status has a significant biological impact on tumor tissues and may be relevant to cancer development and progression.
CLINICAL EPIGENETICS
(2023)
Article
Oncology
Melanie K. Prodhomme, Roxane M. Pommier, Camille Franchet, Frederique Fauvet, Valerie Bergoglio, Pierre Brousset, Anne-Pierre Morel, Anne-Cecile Brunac, Mojgan Devouassoux-Shisheboran, Virginie Petrilli, Caroline Moyret-Lalle, Jean-Sebastien Hoffmann, Alain Puisieux, Agnes Tissier
Summary: The study demonstrated that ZEB1 represses the expression of POLQ, inhibiting TMEJ activity and controlling genome integrity in breast cancer cells. This reveals an original mechanism of TMEJ regulation and highlights ZEB1 as a key player in maintaining genome stability during cancer progression.
Article
Biochemistry & Molecular Biology
Huimin Hu, Xiaodong Wang, Yansheng Huang, Baorong He, Jinwen Zhu, Kai Sun, Chaoyang Deng, Yunshan Guo, Dingjun Hao, Bin Jian
Summary: The natural compound obacunone found in citrus fruits can inhibit osteoclast differentiation through modulating the Integrin-FAK-Src pathway, suggesting its potential as a therapeutic candidate for the treatment and prevention of bone diseases such as osteoporosis.
Article
Biotechnology & Applied Microbiology
Qian Liu, Madison Reed, Haiying Zhu, Yan Cheng, Joana Almeida, Gema Fruhbeck, Ricardo Ribeiro, Pingzhao Hu
Summary: This study aimed to identify epitranscriptomic biomarkers for distinguishing between localized prostate cancer (LPC) and locally advanced prostate cancer (LAPC). Through integrative analysis of gene expression and DNA methylation, a gene signature was discovered which showed promising results in classifying different stages of prostate cancer.
Article
Biochemistry & Molecular Biology
Keun-Yeong Jeong, Seon Young Park, Min Hee Park, Hwan Mook Kim
Summary: Calcium supply can lead to the degradation of Src protein, reducing the survival signals in triple-negative breast cancer cells, thus showing potential as an anti-cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Peien Wang, Haijiang Qu, Lin Wang, Zhe Hu
Summary: The study investigated the role of circUSPL1 in breast cancer (BC) progression and found that it regulates BC cell proliferation, migration, invasion, and glycolysis. CircUSPL1 targets miR-1296-5p and downregulates MTA1, thereby inhibiting BC cell malignant phenotypes. This research provides a theoretical basis for BC treatment.
Article
Oncology
Jodi M. Saunus, Xavier M. De Luca, Korinne Northwood, Ashwini Raghavendra, Alexander Hasson, Amy E. McCart Reed, Malcolm Lim, Samir Lal, A. Cristina Vargas, Jamie R. Kutasovic, Andrew J. Dalley, Mariska Miranda, Emarene Kalaw, Priyakshi Kalita-de Croft, Irma Gresshoff, Fares Al-Ejeh, Julia M. W. Gee, Chris Ormandy, Kum Kum Khanna, Jonathan Beesley, Georgia Chenevix-Trench, Andrew R. Green, Emad A. Rakha, Ian O. Ellis, Dan V. Nicolau, Peter T. Simpson, Sunil R. Lakhani
Summary: This study reveals the relevance of SOX10 gene in triple-negative breast cancer (TNBC) and its role in the intratumoral heterogeneity. The researchers found that the reprogramming of SOX10 is associated with genome-wide promoter methylation loss, leading to a more primitive phenotype in TNBC.
Article
Biochemistry & Molecular Biology
Chia- Lin, Shie-Shan Wang, Chien-Hui Hung, Pey-Jium Chang, Lee-Wen Chen
Summary: The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded ORF50 protein negatively regulates MDM2 expression through repressing Sp1- and p53-mediated transactivation. This reciprocal negative regulation between ORF50 and MDM2 provides insights into the regulatory mechanisms involved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Idir Malki, Inara Liepina, Nora Kogelnik, Hollie Watmuff, Sue Robinson, Adam Lightfoot, Oksana Gonchar, Andrew Bottrill, Andrew M. Fry, Cyril Dominguez
Summary: In this study, we comprehensively investigated the post-translational modifications of Sam68 protein at different stages of the cell cycle using mass spectrometry, nuclear magnetic resonance spectroscopy, and cell biology techniques. We found that Sam68 is specifically phosphorylated at T33 and T371 by Cdk1, which reduces its RNA binding ability, controls its cellular localization, and decreases its alternative splicing activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Ecology
Man-Young Jung, Christopher J. Sedlacek, K. Dimitri Kits, Anna J. Mueller, Sung-Keun Rhee, Linda Hink, Graeme W. Nicol, Barbara Bayer, Laura Lehtovirta-Morley, Chloe Wright, Jose R. de la Torre, Craig W. Herbold, Petra Pjevac, Holger Daims, Michael Wagner
Summary: This study characterized the ammonia oxidation kinetic properties of 12 AOA, finding that Nitrosocosmicus species have the lowest affinity for ammonia and total ammonium among all characterized AOA. The substrate affinity of ammonia oxidizers is correlated with their cell surface area to volume ratios, and ammonia-not ammonium-is the substrate for the ammonia monooxygenase enzyme of AOA and comammox, which is similar to AOB.
Article
Biochemistry & Molecular Biology
Shams Twafra, Chana G. Sokolik, Tal Sneh, Kolluru D. Srikanth, Tomer Meirson, Alessandro Genna, Jordan H. Chill, Hava Gil-Henn
Summary: The dissemination of cancer cells is a major cause of death in cancer patients, but there is currently no treatment to eradicate metastatic cancer. This study developed a peptide inhibitor that can block the formation and function of invadopodia, reducing the ability of tumor cells to spread and invade. These findings have important implications for the prevention of highly metastatic primary breast tumors and secondary tumors that have already spread to other parts of the body.
Article
Multidisciplinary Sciences
Awatef Allouch, Laurent Voisin, Yanyan Zhang, Syed Qasim Raza, Yann Lecluse, Julien Calvo, Dorothee Selimoglu-Buet, Stephane de Botton, Fawzia Louache, Francoise Pflumio, Eric Solary, Jean-Luc Perfettini
Summary: Targeting the reprogramming and phagocytic capacities of tumor-associated macrophages (TAMs) offers a therapeutic opportunity for cancer treatment. In this study, the authors demonstrate that overexpressing CDKN1A/p21 in engineered macrophages reduces leukemia tumor burden and extends survival in mouse models of T-ALL.
NATURE COMMUNICATIONS
(2022)
Review
Critical Care Medicine
Michael Amoo, Philip J. O'Halloran, Jack Henry, Mohammed Ben Husien, Paul Brennan, Matthew Campbell, John Caird, Gerard F. Curley
Summary: Traumatic brain injury (TBI) is a major cause of death and disability, particularly among young people. The development of secondary brain injury after TBI is mainly due to disruptions in the complex relationship between cells and proteins in the neurovascular unit, or a loss of integrity in the blood-brain barrier (BBB). Changes in the BBB after TBI include loss of tight junction proteins, pericyte loss and migration, and altered expressions of water channel proteins in astrocyte end-feet processes. Research is increasingly focused on identifying biological and radiological biomarkers of BBB dysfunction severity and its impact on outcomes after TBI. This review explores microscopic changes in the neurovascular unit and current radiological methods for evaluating it in pre-clinical and clinical practice.
JOURNAL OF NEUROTRAUMA
(2022)
Article
Clinical Neurology
Philip J. O'Halloran, Anna Cleary, Jane B. Cryan, Alan Beausang, Francesca M. Brett, John Caird
Summary: This study retrospectively investigated melanoma brain metastases (MBM) in Ireland and found that male predominance, leptomeningeal disease, and BRAF mutation are important prognostic factors in this population group.
BRITISH JOURNAL OF NEUROSURGERY
(2022)
Article
Neurosciences
Moumin Mohamed, A. Alamri, M. Mohamed, N. Khalid, Pj O'Halloran, Ve Staartjes, C. Uff
Summary: This study aimed to investigate the potential application of machine learning and convolutional neural networks (CNN) in prognosticating patients with traumatic brain injury (TBI). The results showed that the developed CNN model was able to predict the prognosis of patients by interpreting brain stem injuries.
Article
Oncology
Henry Beetham, Billie G. C. Griffith, Olga Murina, Alexander E. P. Loftus, David A. Parry, Carolin Temps, Jayne Culley, Morwenna Muir, Asier Unciti-Broceta, Andrew H. Sims, Adam Byron, Valerie G. Brunton
Summary: Loss of integrin-linked kinase (ILK) enhances sensitivity to SRC inhibitors in breast cancer, providing a new opportunity for improving the clinical effectiveness of SRC inhibitors.
Article
Medicine, Research & Experimental
Lucia Zhu, Diana Retana, Pedro Garcia-Gomez, Laura Alvaro-Espinosa, Neibla Priego, Mariam Masmudi-Martin, Natalia Yebra, Lauritz Miarka, Elena Hernandez-Encinas, Carmen Blanco-Aparicio, Sonia Martinez, Cecilia Sobrino, Nuria Ajenjo, Maria-Jesus Artiga, Eva Ortega-Paino, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Riccardo Soffietti, Luca Bertero, Paola Cassoni, Tobias Weiss, Javier Munoz, Juan Manuel Sepulveda, Pedro Gonzalez-Leon, Luis Jimenez-Roldan, Luis Miguel Moreno, Olga Esteban, Angel Perez-Nunez, Aurelio Hernandez-Lain, Oscar Toldos, Yolanda Ruano, Lucia Alcazar, Guillermo Blasco, Jose Fernandez-Alen, Eduardo Caleiras, Miguel Lafarga, Diego Megias, Osvaldo Grana-Castro, Carolina Nor, Michael D. Taylor, Leonie S. Young, Damir Vareslija, Nicola Cosgrove, Fergus J. Couch, Lorena Cusso, Manuel Desco, Silvana Mouron, Miguel Quintela-Fandino, Michael Weller, Joaquin Pastor, Manuel Valiente
Summary: We report a medium-throughput drug-screening platform based on organotypic cultures that evaluates inhibitors against metastases growing in situ. Through this approach applied to brain metastasis, vulnerabilities were identified and a blood-brain barrier permeable HSP90 inhibitor was found to be effective against mouse and human brain metastases. In situ proteomic analysis revealed a novel molecular program in brain metastasis and potential biomarkers of poor prognosis and resistance mechanisms. This study validates METPlatform as a potent resource for metastasis research and personalized management of metastatic disease.
EMBO MOLECULAR MEDICINE
(2022)
Article
Clinical Neurology
Maeve A. Hennessy, Zachary L. Coyne, Philip J. O'Halloran, William Mullally, Mohamed Dablouk, Stephen MacNally, Patrick G. Morris
Summary: The role of surgical resection in recurrent GBM is still unclear. This study investigated the survival outcomes and prognostic factors for patients with recurrent IDH-wildtype GBM who underwent surgical reresection. The findings showed that MGMT methylation, late re-resection, younger age, and higher Karnofsky Performance Status were associated with improved overall survival. However, the extent of re-resection did not reach statistical significance. Reresection could be considered for carefully selected cases with good performance status.
JOURNAL OF CLINICAL NEUROSCIENCE
(2022)
Review
Clinical Neurology
Michael Amoo, Jack Henry, Philip J. O'Halloran, Paul Brennan, Mohammed Ben Husien, Matthew Campbell, John Caird, Mohsen Javadpour, Gerard F. Curley
Summary: S100B showed optimal sensitivity and specificity at a threshold of 0.72 μg/L, while GFAP demonstrated 71% sensitivity and specificity at 626 pg/mL, with sensitivity peaking at 93% at 22 pg/mL. Further investigation is needed to explore the potential advantages of GFAP in the screening of mild TBI.
NEUROSURGICAL REVIEW
(2022)
Article
Multidisciplinary Sciences
Nicola Cosgrove, Damir Vareslija, Stephen Keelan, Ashuvinee Elangovan, Jennifer M. Atkinson, Sinead Cocchiglia, Fiona T. Bane, Vikrant Singh, Simon Furney, Chunling Hu, Jodi M. Carter, Steven N. Hart, Siddhartha Yadav, Matthew P. Goetz, Arnold D. K. Hill, Steffi Oesterreich, Adrian Lee, Fergus J. Couch, Leonie S. Young
Summary: The authors conducted a comprehensive study on the molecular landscape of breast cancer brain metastases, focusing on different breast cancer subtypes. They identified homologous recombination deficiency as a significant therapeutic vulnerability. The study revealed distinct transcriptional programs enriched in brain metastases and identified important hub genes and functional processes associated with the disease.
NATURE COMMUNICATIONS
(2022)
Correction
Biotechnology & Applied Microbiology
Preeti Borde, Nicola Cosgrove, Sara Charmsaz, Stephen T. T. Safrany, Leonie Young
CANCER GENE THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Preeti Borde, Nicola Cosgrove, Sara Charmsaz, Stephen T. Safrany, Leonie Young
Summary: Therapeutic options and prognostic biomarkers for hormone receptor- or Her2 receptor-negative breast cancers are limited. This study reveals that the sigma-1 receptor is elevated in breast cancer, particularly in the aggressive triple-negative subtype. High SIGMAR1 expression is associated with poor survival outcomes and shorter survival times in ER-Her2- groups. In addition, higher SIGMAR1 levels are related to a higher rate of pathologic complete response in patients receiving neoadjuvant taxane + anthracycline treatment.
CANCER GENE THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Fuhui Chen, Sevim B. Gurler, David Novo, Cigdem Selli, Denis G. Alferez, Secil Eroglu, Kyriaki Pavlou, Jingwei Zhang, Andrew H. Sims, Neil E. Humphreys, Antony Adamson, Andrew Campbell, Owen J. Sansom, Cathy Tournier, Robert B. Clarke, Keith Brennan, Charles H. Streuli, Ahmet Ucar
Summary: Breast cancer stem cells (BCSC), responsible for treatment resistance, tumor recurrence, and metastasis, have been hindered by heterogeneity and lack of selective molecular targets. This study identifies RAC1B as a clinically relevant molecular target for BCSC-targeting therapies, highlighting its role in the maintenance of BCSC and their chemoresistance to doxorubicin.
Article
Cell Biology
Marie-Claire Fitzgerald, Philip J. O'Halloran, Sean A. Kerrane, Triona Ni Chonghaile, Niamh M. C. Connolly, Brona M. Murphy
Summary: Systems-level analysis of apoptosis protein expression and signaling interactions can differentiate between medulloblastoma cell lines with different responses to chemotherapy. BCL-XL and MCL-1 were identified as key anti-apoptotic proteins in medulloblastoma, with distinct protective roles. We provide rationale for further evaluation of BCL-XL and MCL-1 inhibitors in medulloblastoma treatment.
CELL DEATH & DISEASE
(2023)
Article
Clinical Neurology
M. Creedon, H. Humphreys, R. Connolly, L. Gaughan, M. Skally, J. Caird, J. Duddy, P. J. O'Halloran, T. Mandiwanza, K. Burns, B. Dinesh, E. Smyth, K. O'Connell, F. Fitzpatrick
Summary: The multi-disciplinary approach in neurosurgical prescribing was beneficial in reducing antimicrobial use. Most antimicrobial prescriptions were deemed appropriate and stewardship actions were implemented. Neurosurgical doctors found the antimicrobial stewardship discussions helpful for education on antibiotic prescribing.