Review
Oncology
Acharya Balkrishna, Rashmi Mittal, Vedpriya Arya
Summary: This review summarizes the role of miRNA in triple-negative breast cancer, suggesting that miRNA can inhibit metastatic cascade through various mechanisms and may serve as prognostic and metastatic biomarkers.
CURRENT CANCER DRUG TARGETS
(2021)
Article
Oncology
Dominika Radomska, Robert Czarnomysy, Anna Szymanowska, Dominik Radomski, Enrique Dominguez-Alvarez, Anna Bielawska, Krzysztof Bielawski
Summary: This study evaluated the anticancer activity of novel selenoesters in breast cancer cells, and the results showed that these compounds exhibited high cytotoxicity, induced apoptosis and autophagy, and hindered the cell cycle. These findings suggest that selenium-containing compounds have significant potential as candidates for anticancer agents.
Article
Oncology
Zheng Fang, Hong-yu Shen, Qi Xu, Hong-lei Zhou, Lei Li, Si-Yuan Yang, Zhen Zhu, Jin-hai Tang
Summary: Breast cancer patients with high expression of PUS1 have poor prognosis and shorter survival time. Knockdown of PUS1 suppresses the proliferation, colony formation, and invasion abilities of breast cancer cells. PUS1 may serve as a promising biomarker and treatment target for breast cancer.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Peter Smyth, Jutharat Sasiwachirangkul, Rich Williams, Christopher J. Scott
Summary: This review provides an overview of the distinctive properties and roles of cathepsin S (CTSS) within the lysosomal cysteine cathepsin family. It highlights the various pathologies in which CTSS has been implicated and provides an update on the clinical progress towards specific inhibitors. CTSS is considered a significant biomarker and potential therapeutic target.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Oncology
Meng-Yuan Wang, Man Huang, Chao-Yi Wang, Xiao-Ying Tang, Jian-Gen Wang, Yong-De Yang, Xin Xiong, Chao-Wei Gao
Summary: This study identified 189 fusion transcripts in TNBC, with 22 recurrent fusions. The distribution of fusion events in TNBC varied among subtypes, with more events on chromosomes 11 and 19. MFGE8-HAPLN3 was selected as a potential biomarker in TNBC, and its critical role was further validated.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Wenting Peng, Caijin Lin, Shanshan Jing, Guanhua Su, Xi Jin, Genhong Di, Zhiming Shao
Summary: This study established clinical prognostic model, seven-gene signature, and combined model for predicting distant metastasis risk in lymph node-negative TNBC patients. The seven-gene signature showed significant differentiation of distant metastasis risk in both training and validation sets. The composite clinical and gene signature demonstrated improved prognostic accuracy compared to the clinical signature.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Kaushik Das, Subhojit Paul, Arnab Ghosh, Saurabh Gupta, Tanmoy Mukherjee, Prem Shankar, Anshul Sharma, Shiva Keshava, Subhash C. Chauhan, Vivek Kumar Kashyap, Deepak Parashar
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks specific molecular targets for treatment. Chemotherapy is the main systemic treatment for TNBC, but its efficacy varies and resistance is common. TNBC has a high mutational burden and is considered the most immunogenic subtype of breast cancer. Recent evidence suggests that extracellular vesicles (EVs) play a significant role in TNBC immunotherapy.
Review
Oncology
Lin He, Neda Wick, Sharon Koorse Germans, Yan Peng
Summary: Triple negative breast cancer lacks targeted therapies and has poor prognosis. Chemotherapy is the main treatment, but recent advances have shown the importance of breast cancer stem cells in tumor initiation, metastasis, and chemoresistance. Targeting breast cancer stem cells may lead to new therapies that can improve patient survival rates.
Article
Oncology
Marine Lemesle, Marine Geoffroy, Fabien Alpy, Catherine-Laure Tomasetto, Sandra Kuntz, Isabelle Grillier-Vuissoz
Summary: This study investigated the role of CLDN1 in triple-negative breast cancer (TNBC) and found that CLDN1 can increase the sensitivity of TNBC cells to chemotherapy drugs. The findings support the use of CLDN1 as a predictive marker for chemotherapy response in TNBC.
Article
Biochemistry & Molecular Biology
Shengli Dong, Hassan Yousefi, Isabella Van Savage, Samuel C. Okpechi, Maryl K. Wright, Margarite D. Matossian, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
Summary: Combination therapy with ceritinib and enzalutamide inhibits the growth of AR(+) TNBC cells, while combination therapy with ceritinib and paclitaxel drastically inhibits tumor growth. These findings suggest that combination treatment with these FDA-approved drugs can improve the therapeutic response in both AR-positive and negative breast cancer.
Review
Oncology
Juan Zhang, Qi Tian, Mi Zhang, Hui Wang, Lei Wu, Jin Yang
Summary: Breast cancer is a common female cancer worldwide, with triple-negative breast cancer being one of the most dangerous subtypes with high mortality and relapse rates. Immunotherapy has become a promising and effective treatment, but not all patients are sensitive to it, highlighting the importance of selecting suitable candidates for immunotherapy. Recent discoveries in immune-related factors of TNBC offer insights into predicting prognosis and response to immunotherapy.
Article
Biochemistry & Molecular Biology
Runjie Song, Peilan Guo, Xin Ren, Lijun Zhou, Peng Li, Nafis A. Rahman, Slawomir Wolczynski, Xiru Li, Yanjun Zhang, Mei Liu, Jiali Liu, Xiangdong Li
Summary: This study reanalyzed the circRNA expression data of TNBC and identified circCAPG as a potential biomarker in TNBC. Further experiments showed that circCAPG could encode a novel polypeptide, CAPG-171aa, which promoted the proliferation and metastasis of TNBC cells. Additionally, SLU7 was found to be involved in the formation of circCAPG. These findings provide new insights into the role of circCAPG in TNBC and its potential as a therapeutic target and prognostic biomarker.
Article
Biochemistry & Molecular Biology
Saioa Mendaza, David Guerrero-Setas, Inaki Monreal-Santesteban, Ane Ulazia-Garmendia, Alicia Cordoba Iturriagagoitia, Susana De la Cruz, Esperanza Martin-Sanchez
Summary: A novel DNA methylation signature with potential predictive value for TNBC diagnosis has been discovered. This signature was validated using various samples, confirming its effectiveness in TNBC and BC samples.
Article
Biochemistry & Molecular Biology
Chitra Thakur, Nicholas J. Carruthers, Qian Zhang, Liping Xu, Yao Fu, Zhuoyue Bi, Yiran Qiu, Wenxuan Zhang, Priya Wadgaonkar, Bandar Almutairy, Chunna Guo, Paul M. Stemmer, Fei Chen
Summary: This study comprehensively analyzed the role of mdig in triple-negative breast cancer through proteomic analysis. The results revealed that mdig knockout significantly altered the expression of proteins and pathways associated with breast cancer, highlighting its importance in tumorigenicity and invasiveness.
Article
Multidisciplinary Sciences
Mingda Zhu, Jingyang Zhang, Guangyu Li, Zhenzhen Liu
Summary: A key enhancer RNA region (ELOVL2-AS1) in breast cancer (BRCA) was identified through integrated analysis, which showed a direct regulatory interaction with ELOVL2 gene and lower expression in triple negative breast cancer (TNBC).
Article
Critical Care Medicine
Michael C. McKelvey, Anthony A. Abladey, Donna M. Small, Declan F. Doherty, Richard Williams, Aaron Scott, C. Arnold Spek, Keren S. Borensztajn, Leslie Holsinger, Robert Booth, Cecilia M. O'Kane, Daniel F. McAuley, Clifford C. Taggart, Sinead Weldon
Summary: This study investigates the role of cathepsin S in acute respiratory distress syndrome (ARDS), a condition without specific pharmacological treatments. The results show that cathepsin S contributes to acute lung injury and could be a potential therapeutic target for ARDS. The study demonstrates that elevated cathepsin S activity and concentration are associated with acute lung inflammation, leading to neutrophil recruitment and protein leakage. Additionally, the study suggests that cathepsin S mediates its pathogenic effects partly through protease-activated receptor-1.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jia Lin, Aidan P. McCann, Naphannop Sereesongsaeng, Jonathan M. Burden, Alhareth A. Alsa'd, Roberta E. Burden, Ileana Micu, Richard Williams, Sandra Van Schaeybroeck, Emma Evergren, Paul Mullan, Jeremy C. Simpson, Christopher J. Scott, James F. Burrows
Summary: Expression of the deubiquitinase USP17 is induced by various stimuli and it plays important roles in cell functions, including regulation of lysosome positioning and trafficking, lysosomal protease secretion, and plasma membrane repair.
Article
Cell Biology
Ada-Sophia Clees, Verena Stolp, Bjoern Haeupl, Dominik C. Fuhrmann, Frank Wempe, Marcel Seibert, Sarah Weber, Antje Banning, Ritva Tikkanen, Richard Williams, Bernhard Bruene, Hubert Serve, Frank Schnuetgen, Ivana von Metzler, Nina Kurrle
Summary: The study analyzed the adaptation of multiple myeloma cells to hypoxia, revealing changes in protein expression and regulation of specific proteins under hypoxic conditions, including the cysteine protease LGMN, which can impact the growth of multiple myeloma cells in hypoxic environments.
Article
Oncology
Hajrah Khawaja, Rebecca Briggs, Cheryl H. Latimer, Mustasin Rassel, Dary Griffin, Lyndsey Hanson, Alberto Bardelli, Frederica Di Nicolantonio, Simon S. McDade, Christopher J. Scott, Shauna Lambe, Manisha Maurya, Andreas U. Lindner, Jochen H. M. Prehn, Jose Sousa, Chris Winnington, Melissa J. LaBonte, Sarah Ross, Sandra Van Schaeybroeck
Summary: Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant colorectal cancer. In this study, researchers found that the combination of AZ'1569 and a Bcl-xL inhibitor led to a dramatic and universal apoptosis, suggesting a potential therapeutic strategy for patients with KRAS G12C-mutant colorectal cancer.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Srikanth Dudem, Pei Xin Boon, Nicholas Mullins, Heather McClafferty, Michael J. Shipston, Richard D. A. Wilkinson, Ian Lobb, Gerard P. Sergeant, Keith D. Thornbury, Irina G. Tikhonova, Mark A. Hollywood
Summary: In this study, the researchers found that LINGO2 plays a role in modulating BK channels. Coexpression of LINGO2 and BK channels resulted in rapid inactivating currents with shifted activation compared to BK alpha currents. The oxidation of BK:LINGO2 currents abolished inactivation, and this effect was resistant to treatment with a reducing agent specific for cysteine residues. The molecular modeling further revealed that methionine oxidation reduces the lipophilicity of the LINGO2 tail, preventing it from occluding the pore of BK channels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Peter Smyth, Jutharat Sasiwachirangkul, Rich Williams, Christopher J. Scott
Summary: This review provides an overview of the distinctive properties and roles of cathepsin S (CTSS) within the lysosomal cysteine cathepsin family. It highlights the various pathologies in which CTSS has been implicated and provides an update on the clinical progress towards specific inhibitors. CTSS is considered a significant biomarker and potential therapeutic target.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Oncology
Sean P. Kennedy, Oliver Treacy, Emma H. Allott, Alex J. Eustace, Niamh Lynam-Lennon, Niamh Buckley, Tracy Robson
Summary: Innovation in both detection and treatment of cancer is crucial for improving therapeutic strategies, especially for patients with new or resistant variants of cancer. By advancing our understanding of cancer biology, early detection and novel therapeutic approaches can be informed, leading to a more comprehensive and thorough intervention on cancer.
Article
Polymer Science
Achmad Himawan, Qonita Kurnia Anjani, Usanee Detamornrat, Lalitkumar K. Vora, Andi Dian Permana, Rand Ghanma, Yara Naser, Dina Rahmawanty, Christopher J. Scott, Ryan F. Donnelly
Summary: The characteristics of multifunctional polymeric hydrogel-forming microarray patches based on poly(vinyl alcohol)/poly(vinylpyrrolidone)/citric acid composite crosslinked at 80 degrees C were investigated. The swelling study showed that this composite possesses a higher swelling degree than the same polymer heated at 130 degrees C due to a lower crosslink density, which was then confirmed by FTIR examination. The patch can function both as a means to sample model hydrophilic drugs from the skin and to deliver them when combined with a melt-type polyethylene glycol reservoir.
EUROPEAN POLYMER JOURNAL
(2023)
Editorial Material
Nanoscience & Nanotechnology
Michelle K. Greene, Christopher J. Scott
Summary: The study discovers a new pathway, Siglec-14-DAP12-Syk, through which multi-walled carbon nanotubes induce inflammation and toxicity in human macrophages. The findings also suggest potential pharmacological strategies for controlling this response.
NATURE NANOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Fabien Thoreau, Peter A. Szijj, Michelle K. Greene, Lea N. C. Rochet, Ioanna A. Thanasi, Jaine K. Blayney, Antoine Maruani, James R. Baker, Christopher J. Scott, Vijay Chudasama
Summary: In recent years, there has been growing interest in protein-protein conjugation, especially in the context of bispecific antibodies (bsAbs) and their therapeutic applications. These molecules contain two paratopes capable of binding two distinct epitopes, enabling complex biological functions that monospecific antibodies cannot achieve. While traditional methods for bsAb construction involve protein engineering, recent developments have led to the emergence of chemical methods that offer increased modularity, speed, and the potential for further functionalization. However, most of these approaches lack the inclusion of a fragment crystallizable (Fc) modality, which provides effector function and increased half-life. In this study, a novel method using disulfide rebridging and click-chemistry has been reported for the generation of Fc-containing, IgG-like mono- and bispecific antibodies, referred to as synthetic antibodies (SynAbs). A T cell engager SynAb, FcCD20-(FabHER2)-FabCD3, has been successfully constructed and demonstrated the expected biological functions, including the ability to effectively kill HER2+ target cells in co-culture assays with T cells.
ACS CENTRAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Naphannop Sereesongsaeng, James F. Burrows, Christopher J. Scott, Klaudia Brix, Roberta E. Burden
Summary: Our study found that CTSV has an impact on breast cancer cell proliferation, with depleted CTSV cells showing delayed progression through the G2/M phase of the cell cycle. Further investigation revealed that CTSV can regulate the expression levels of histones H3 and H4 in the nucleus by controlling the expression of their chaperone protein sNASP. We also discovered that CTSV is localized in the nuclear compartment of breast tumor cells and is required for cell cycle progression and histone stability.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Materials Science, Biomaterials
Adam Leach, Marie Finnegan, Mariana S. Machado, Laura Ferguson, John Steven, Peter Smyth, Andrew Porter, Caroline Barelle, Efrosyni Themistou, Christopher J. Scott
Summary: This study focuses on the development of actively targeted drug loaded nanoparticles for cancer and other diseases. A new polymer was synthesized and modified to allow the attachment of targeting ligands. The resulting nanoparticles showed specific affinity to their target antigen and have potential for therapeutic development.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Health Policy & Services
Mark Lawler, Richard Sullivan, Ghassan K. Abou-Alfa, Karen McCloskey, Debbie Keatley, Jennifer Feighan, William Dahut, Eibhlin Mulroe, Robert Ladner, Mohamed Genead, Maeve Lowery, James L. Gulley, Christopher J. Scott, Daniel B. Longley, Aedin Culhane, William M. Gallagher, Nick Orr, Stephen J. Chanock, Satish Gopal
Summary: The Good Friday Agreement has had a positive impact on peace and reconciliation, as well as cancer research and care in Ireland. The creation of the Ireland - Northern Ireland - National Cancer Institute Cancer Consortium has fostered collaboration between researchers, physicians, and healthcare professionals, leading to improved research, patient care, and innovation.
JOURNAL OF CANCER POLICY
(2023)
Article
Chemistry, Multidisciplinary
Shannon R. Tracey, Peter Smyth, Una M. Herron, James F. Burrows, Andrew J. Porter, Caroline J. Barelle, Christopher J. Scott
Summary: Intracellular delivery of proteins, peptides and biologics is an emerging field, and researchers have developed a cationic nanoparticle delivery system using a polyethyleneimine and poly-(lactic-co-glycolic acid) polymer blend, which successfully delivers Variable New Antigen Receptors (vNARs) intracellularly.