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"Lee, Ann"
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DNA methylation in breast cancer: early detection and biomarker discovery through current and emerging approaches
Breast cancer remains one of the most common cancers in women worldwide. Early detection is critical for improving patient outcomes, yet current screening methods have limitations. Therefore, there is a pressing need for more sensitive and specific approaches to detect breast cancer in its earliest stages. Liquid biopsy has emerged as a promising non-invasive method for early cancer detection and management. DNA methylation, an epigenetic alteration that often precedes genetic changes, has been observed in precancerous or early cancer stages, making it a valuable biomarker. This review explores the role of DNA methylation in breast cancer and its potential for developing blood-based tests. We discuss advancements in DNA methylation detection methods, recent discoveries of potential DNA methylation biomarkers from both single-omics and multi-omics integration studies, and the role of machine learning in enhancing diagnostic accuracy. Challenges and future directions are also addressed. Although challenges remain, advances in multi-omics integration and machine learning continue to enhance the clinical potential of methylation-based biomarkers. Ongoing research is crucial to further refine these approaches and improve early detection and patient outcomes.
Journal Article
“Smells like team spirit” the association between running club membership and performance in the London Marathon: An economic analysis
This study examines the association between club membership and marathon performance using a dataset of 206,653 London Marathon runners. Our results show a statistically significant association between club membership and marathon performance for both males and females which sees club membership potentially mitigating pace decline with age and resulting in substantial improvements in finishing times of up to 40 minutes. We implement a production function framework and align with three principles of economic organisation. The findings have relevance for marathon participants, coaches, and athletic associations as well as implications beyond athletics to other sports or cooperative activities.
Journal Article
Development and validation of a circulating microRNA panel for the early detection of breast cancer
BackgroundMammography is widely used for breast cancer screening but suffers from a high false-positive rate. Here, we perform the largest comprehensive, multi-center study to date involving diverse ethnic groups, for the identification of circulating miRNAs for breast cancer screening.MethodsThis study had a discovery phase (n = 289) and two validation phases (n = 374 and n = 379). Quantitative PCR profiling of 324 miRNAs was performed on serum samples from breast cancer (all stages) and healthy subjects to identify miRNA biomarkers. Two-fold cross-validation was used for building and optimising breast cancer-associated miRNA panels. An optimal panel was validated in cohorts with Caucasian and Asian samples. Diagnostic ability was evaluated using area under the curve (AUC) analysis.ResultsThe study identified and validated 30 miRNAs dysregulated in breast cancer. An optimised eight-miRNA panel showed consistent performance in all cohorts and was successfully validated with AUC, accuracy, sensitivity, and specificity of 0.915, 82.3%, 72.2% and 91.5%, respectively. The prediction model detected breast cancer in both Caucasian and Asian populations with AUCs ranging from 0.880 to 0.973, including pre-malignant lesions (stage 0; AUC of 0.831) and early-stage (stages I–II) cancers (AUC of 0.916).ConclusionsOur panel can potentially be used for breast cancer screening, in conjunction with mammography.
Journal Article
Functions of double‐negative B cells in autoimmune diseases, infections, and cancers
Most mature B cells can be divided into four subtypes based on the expression of the surface markers IgD and CD27: IgD
+
CD27
−
naïve B cells, IgD
+
CD27
+
unswitched memory B cells, IgD
−
CD27
+
switched memory B cells, and IgD
−
CD27
−
double‐negative (DN) B cells. Despite their small population size in normal peripheral blood, DN B cells play integral roles in various diseases. For example, they generate autoimmunity in autoimmune conditions, while these cells may generate both autoimmune and antipathogenic responses in COVID‐19, or act in a purely antipathogenic capacity in malaria. Recently, DN B cells have been identified in nasopharyngeal carcinoma and non‐small‐cell lung cancers, where they may play an immunosuppressive role. The distinct functions that DN B cells play in different diseases suggest that they are a heterogeneous B‐cell population. Therefore, further study of the mechanisms underlying the involvement of DN B cells in these diseases is essential for understanding their pathogenesis and the development of therapeutic strategies. Further research is thus warranted to characterize the DN B‐cell population in detail.
Graphical Abstract
This review discusses the functions of double‐negative B cells in different diseases.
Journal Article
Effects of the pan-caspase inhibitor Q-VD-OPh on human neutrophil lifespan and function
Human neutrophils are abundant, short-lived leukocytes that turn over at a rate of approximately 10 11 cells/day via a constitutive apoptosis program. Certain growth factors, inflammatory mediators and infectious agents can delay apoptosis or induce neutrophils to die by other mechanisms. Nonetheless, a large body of data demonstrates that apoptosis of untreated neutrophils typically ensues within 24 hours of cell isolation and in vitro culture. At the molecular level apoptosis is driven by executioner caspase-3, and during this process cell proinflammatory capacity and host defense functions are downregulated. We undertook the current study to determine the extent to which human neutrophil viability and function could be prolonged by treatment with the non-toxic, irreversible, pan-caspase inhibitor Q-VD-OPh. Our data demonstrate that a single 10 μM dose of this drug was sufficient to markedly prolong cell lifespan. Specifically, we show that apoptosis was prevented for at least 5 days as indicated by analysis of nuclear morphology, DNA fragmentation, and phosphatidylserine externalization together with measurements of procaspase-3 processing and caspase activity. Conversely, mitochondrial depolarization declined despite abundant Myeloid Cell Leukemia 1 (MCL-1). At the same time, glutathione levels were maintained and Q-VD-OPh prevented age-associated increases mitochondrial oxidative stress. Regarding functional capacity, we show that phagocytosis, NADPH oxidase activity, chemotaxis, and degranulation were maintained following Q-VD-OPh treatment, albeit to somewhat different extents. Thus, a single 10 μM dose of Q-VD-OPh can sustain human neutrophil viability and function for at least 5 days.
Journal Article