Publications by authors named "K Hun Mok"

375 Publications

Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex.

Nat Commun 2021 06 8;12(1):3427. Epub 2021 Jun 8.

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Lund, Sweden.

Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
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http://dx.doi.org/10.1038/s41467-021-23748-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187399PMC
June 2021

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening.

Scand J Clin Lab Invest 2021 Jun 1:1-8. Epub 2021 Jun 1.

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to -112.8%] and -23.3% [95%CI -41.9% to -4.7%]. Passing-Bablok indicated significant systematic (-2.78 [95%CI -3.57 to -2.04]) and proportional bias (1.30 [95%CI 1.15 to -1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65-0.78]) between inhibin-A assays. The uE3 and inhibin-A log MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and -0.0001 [SD = 0.2078], and -0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81-83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.
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http://dx.doi.org/10.1080/00365513.2021.1929439DOI Listing
June 2021

Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging.

Alzheimers Dement 2021 May 25. Epub 2021 May 25.

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.

Introduction: Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD.

Methods: We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.

Results: We identified 429 proteins that were dysregulated in AD plasma. We selected 19 "hub proteins" representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve  = 0.9690-0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages.

Discussion: This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.
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http://dx.doi.org/10.1002/alz.12369DOI Listing
May 2021

Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging.

Alzheimers Dement 2021 May 25. Epub 2021 May 25.

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.

Introduction: Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD.

Methods: We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.

Results: We identified 429 proteins that were dysregulated in AD plasma. We selected 19 "hub proteins" representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve  = 0.9690-0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages.

Discussion: This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.
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http://dx.doi.org/10.1002/alz.12369DOI Listing
May 2021

Effects of Gasterophilus pecorum infestation on the intestinal microbiota of the rewilded Przewalski's horses in China.

PLoS One 2021 11;16(5):e0251512. Epub 2021 May 11.

Department of Civil and Environmental Engineering, University of Macau, Macao, China.

Horse botflies have been a threat to the Przewalski's horses in the Kalamaili Nature Reserve in Xinjiang of China since their reintroduction to the original range. As larvae of these parasites could infest the intestine of a horse for months, they could interact with and alter the structure and composition of its intestinal microbiota, affecting adversely its health. Nonetheless, there are no such studies on the rewilded Przewalski's horses yet. For the first time, this study characterizes the composition of the intestinal microbiota of 7 rewilded Przewalski's horses infected severely by Gasterophilus pecorum following and prior to their anthelmintic treatment. Bioinformatics analyses of the sequence data obtained by amplicon high throughput sequencing of bacterial 16S rRNA genes showed that G. pecorum infestation significantly increased the richness of the intestinal microbial community but not its diversity. Firmicutes and Bacteroidetes were found the dominant phyla as in other animals, and the parasitic infestation decreased the F/B ratio largely by over 50%. Large reduction in relative abundances of the two genera Streptococcus and Lactobacillus observed with G. pecorum infestation suggested possible changes in colic and digestion related conditions of the infected horses. Variations on the relative abundance of the genus groups known to be pathogenic or symbiotic showed that adverse impact of the G. pecorum infestation could be associated with reduction of the symbiotic genera Lactobacillus and Bifidobacterium that are probiotics and able to promote immunity against parasitic infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251512PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112688PMC
May 2021