Publications by authors named "S W S Leung"

2,212 Publications

  • Page 1 of 1

Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.

Clin Cancer Res 2023 Sep 13:OF1-OF16. Epub 2023 Sep 13.

Department of Pediatrics, University of California San Francisco, San Francisco, California.

Purpose: Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes.

Experimental Design: Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model.

Results: PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden.

Conclusions: The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.
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http://dx.doi.org/10.1158/1078-0432.CCR-23-0873DOI Listing
September 2023

Maximising the cost-effectiveness of human papillomavirus testing for cervical screening in the context of routine HPV vaccination in Hong Kong: abridged secondary publication.

Hong Kong Med J 2023 Aug;29 Suppl 4(4):11-15

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

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August 2023

Transcription Factor NFE2L1 Decreases in Glomerulonephropathies after Podocyte Damage.

Cells 2023 Aug 29;12(17). Epub 2023 Aug 29.

School of Medicine, University of St Andrews, St Andrews KY16 9TF, UK.

Podocyte cellular injury and detachment from glomerular capillaries constitute a critical factor contributing to kidney disease. Notably, transcription factors are instrumental in maintaining podocyte differentiation and homeostasis. This study explores the hitherto uninvestigated expression of Nuclear Factor Erythroid 2-related Factor 1 (NFE2L1) in podocytes. We evaluated the podocyte expression of NFE2L1, Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2), and NAD(P)H:quinone Oxidoreductase (NQO1) in 127 human glomerular disease biopsies using multiplexed immunofluorescence and image analysis. We found that both NFE2L1 and NQO1 expressions were significantly diminished across all observed renal diseases. Furthermore, we exposed human immortalized podocytes and ex vivo kidney slices to Puromycin Aminonucleoside (PAN) and characterized the NFE2L1 protein isoform expression. PAN treatment led to a reduction in the nuclear expression of NFE2L1 in ex vivo kidney slices and podocytes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487238PMC
http://dx.doi.org/10.3390/cells12172165DOI Listing
August 2023

Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes.

J Clin Oncol 2023 Sep;41(26):4192-4199

From the Lineberger Comprehensive Cancer Center and Departments of Genetics, Pathology and Laboratory Medicine, and Department of Statistics and Operations Research, Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Pathology, University of Utah Health Sciences Center; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT; Genetic Pathology Evaluation Centre, Department of Pathology, Vancouver Coastal Health Research Institute; Departments of Pathology and Radiation Oncology, British Columbia Cancer Agency; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Genome Sequencing Facility and Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO; and Department of Pathology, Thomas Jefferson University, Philadelphia, PA.

Purpose: To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression-based "intrinsic" subtypes luminal A, luminal B, HER2-enriched, and basal-like.

Methods: A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen.

Results: The intrinsic subtypes as discrete entities showed prognostic significance ( = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%.

Conclusion: Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.
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http://dx.doi.org/10.1200/JCO.22.02511DOI Listing
September 2023

Combined endoscopic sinus surgery and endonasal septal perforation repair: Symptom outcomes and perforation closure rates.

Int Forum Allergy Rhinol 2023 Sep 5. Epub 2023 Sep 5.

Department of Otolaryngology-Head & Neck Surgery, Mayo Clinic in Arizona, Phoenix, Arizona, USA.

Combined endoscopic sinus surgery and nasal septal perforation repair is technically feasible. NOSE-Perf is a recently developed patient-reported outcome measure for nasal septal perforation. The decision to perform combined ESS and NSP repair should be made on a case-by-case basis.
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http://dx.doi.org/10.1002/alr.23265DOI Listing
September 2023
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