Bethany M. Anderson

Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial

Frank A. Vicini, Kathryn Winter, Gary M. Freedman, Douglas W. Arthur et autres

PURPOSE For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI …

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Probing the activity of cysteine cathepsins in inflammatory bowel diseases

Bethany M. Anderson, A. Ziegler, Rhiannon I. Campden, Hongyi Wu et autres

Cathepsin S is a cysteine protease that has been implicated in inflammatory bowel diseases (IBD) for its ability to promote visceral pain. Given its pro-inflammatory roles, we hypothesized that cathepsin S would drive other symptoms associated with IBD. Using activity-based probes, we …

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PfK13-associated artemisinin resistance slows drug activation and enhances antioxidant defence, which can be overcome with sulforaphane

Ghizal Siddiqui, Carlo Giannangelo, Natalie A. Counihan, Yudong Zhou et autres

Abstract Artemisinin resistance is globally prevalent, including in Africa, raising concerns and highlighting the need to better understand the cellular mechanisms behind this resistance. In Plasmodium falciparum , artemisinin resistance is primarily attributed to mutations in the PfKelch13 (PfK13) gene. In this …

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Probing the activity of cysteine cathepsins in inflammatory bowel diseases

Bethany M. Anderson, A. Ziegler, Rhiannon I. Campden, Hongyi Wu et autres

Abstract Cathepsin S is a cysteine protease that has been implicated in inflammatory bowel diseases (IBD) for its ability to promote visceral pain. Given its pro-inflammatory roles, we hypothesized that cathepsin S would drive other symptoms associated with IBD. Using activity-based probes, …

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Legumain drives processing of cathepsins and nuclear localisation of cathepsin L

A. Ziegler, Bangyan Xu, Bethany M. Anderson, L. Y. Liu et autres

Abstract Lysosomal proteases such as the cathepsin family and the asparaginyl endopeptidase, legumain, govern vital processes to maintain cellular proteostasis, and their dysregulation contributes to diverse pathologies. Recent studies have reported extra-lysosomal localisation of these proteases, especially in the nucleus, cytoplasm, and …

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N‐terminomics profiling of naïve and inflamed murine colon reveals proteolytic signatures of legumain

A. Ziegler, Bethany M. Anderson, Rocco Latorre, Rachel M. McQuade et autres

Legumain is a cysteine protease broadly associated with inflammation. It has been reported to cleave and activate protease-activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain …

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TLR9‐dependent dendritic cell maturation promotes IL‐6‐mediated upregulation of cathepsin X

Bangyan Xu, Bethany M. Anderson, Justine D. Mintern, Laura E. Edgington‐Mitchell

Cysteine cathepsins are lysosomal proteases subject to dynamic regulation within antigen-presenting cells during the immune response and associated diseases. To investigate the regulation of cathepsin X, a carboxy-mono-exopeptidase, during maturation of dendritic cells (DCs), we exposed immortalized mouse DCs to various Toll-like …

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Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate

Bangyan Xu, Bethany M. Anderson, Simon J. Mountford, Philip E. Thompson et autres

Proteases function within sophisticated networks. Altering the activity of one protease can have sweeping effects on other proteases, leading to changes in their activity, structure, specificity, localisation, stability, and expression. Using a suite of chemical tools, we investigated the impact of cathepsin …

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Cathepsin S Evokes PAR2-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models

Nguyen Huu Tu, Kenji Inoue, Elyssa Chen, Bethany M. Anderson et autres

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR2) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury …

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Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2

Nguyen Huu Tu, Dane D. Jensen, Bethany M. Anderson, Elyssa Chen et autres

Oral squamous cell carcinoma (OSCC) is one of the most painful cancers, which interferes with orofacial function including talking and eating. We report that legumain (Lgmn) cleaves protease-activated receptor-2 (PAR2) in the acidic OSCC microenvironment to cause pain. Lgmn is a cysteine …

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System-wide biochemical analysis reveals ozonide antimalarials initially act by disrupting Plasmodium falciparum haemoglobin digestion

Carlo Giannangelo, Ghizal Siddiqui, Amanda De Paoli, Bethany M. Anderson et autres

Ozonide antimalarials, OZ277 (arterolane) and OZ439 (artefenomel), are synthetic peroxide-based antimalarials with potent activity against the deadliest malaria parasite, Plasmodium falciparum. Here we used a "multi-omics" workflow, in combination with activity-based protein profiling (ABPP), to demonstrate that peroxide antimalarials initially target the …

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Correction: Novel broad-spectrum activity-based probes to profile malarial cysteine proteases

Michele S. Y. Tan, Dara Davison, Mateo I. Sánchez, Bethany M. Anderson et autres

[This corrects the article DOI: 10.1371/journal.pone.0227341.].