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Kwong, L.

Publications and source records attributed to Kwong, L..

2 recordsLinked to original sources

Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.

cancer biology↗

Effect of sanitation improvements on soil-transmitted helminth eggs in courtyard soil from rural Bangladesh: Evidence from a cluster-randomized controlled trial

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and abundance of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n=419) and control (n=914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and relative egg count reductions (ECR) to compare the prevalence of any STH eggs and arithmetic and geometric mean egg counts for any STH per gram of soil between the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. The arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR=0.98 (95% CI: 0.91-1.05)) or mean egg counts (ECR=0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on environmental reservoirs of STH eggs. In order to effectively reduce the prevalence and abundance of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces. Author summaryImproved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and abundance of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the control and sanitation groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura and hookworm eggs by microscopy. We found no effect of the sanitation intervention on STH eggs in soil. In order to effectively reduce the prevalence and abundance of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces.

ecology↗