Publications by authors named "Ha Thu Le"

Article Synopsis
  • Targeted therapy using tyrosine kinase inhibitors (TKI) can improve survival rates for many patients with non-small cell lung cancer (NSCLC), but resistance to these treatments often develops.
  • A study analyzed the genetic and epigenetic changes in 122 Vietnamese NSCLC patients experiencing resistance to TKI therapy, finding that 41.8% had specific resistance mutations, particularly in the EGFR gene.
  • The research highlighted that the level of genome-wide hypomethylation was linked to how long patients responded to TKI, suggesting that liquid biopsies can help understand TKI resistance mechanisms and inform future treatment strategies.
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Article Synopsis
  • Population-specific profiling of cancer gene mutations is essential for better understanding cancer biology and improving diagnostics and treatment tailored to specific groups.
  • The study used ultra-deep massive parallel sequencing of plasma cell-free DNA (cfDNA) to analyze mutations in 265 Vietnamese patients with advanced non-small cell lung cancer, offering a less invasive alternative to traditional tumor tissue analysis.
  • Although cfDNA testing had lower mutation detection rates, it still identified major mutations in key driver genes that were consistent with findings from tissue sample analysis, highlighting its potential for large-scale genetic profiling in populations with limited access to tumor biopsies.
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Article Synopsis
  • - Comprehensive profiling of mutations in non-small cell lung cancer (NSCLC) is crucial for guiding targeted therapies and improving patient survival, especially in high-incidence regions like Vietnam.
  • - A study involving 350 Vietnamese NSCLC patients identified that mutations in the EGFR gene (35.4%) and KRAS gene (22.6%) were the most common, with notable differences compared to other ethnic cohorts.
  • - The research found that KRAS mutations were more prevalent in males, while EGFR mutations were more frequent in females, and younger patients (<61 years) showed higher rates of ALK and ROS1 rearrangements.
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Article Synopsis
  • Interleukin-17-producing CD4 T helper (Th17) cells play a crucial role in defending against bacterial and fungal infections in the small intestine.
  • Research shows that the number of Th17 cells varies throughout the day, influenced by the circadian rhythm, while this variation is absent in mice with a mutated circadian gene or in abnormal light conditions.
  • The findings highlight the importance of CCL20, a chemokine related to Th17 cell movement, in regulating these daily fluctuations, suggesting potential for improving mucosal vaccination strategies.
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Utilizing our previously reported in silico pharmacophore model for reactivation efficacy of oximes, we present here a discovery of twelve new non-oxime reactivators of diisopropylfluorophosphate (DFP)-inhibited acetylcholinesterase (AChE) obtained through virtual screening of an in-house compound database. Rate constant (kr) efficacy values of the non-oximes were found to be within ten-fold of pralidoxime (2-PAM) in an in vitro DFP inhibited eel AChE assay and one of them showed in vivo efficacy comparable to 2-PAM against brain symptoms for DFP induced neuropathology in guinea pigs. Short listing of the identified compounds were performed on the basis of in silico evaluations for favorable blood brain barrier penetrability, octanol-water partition (Clog P), toxicity (rat oral LD50) and binding affinity to the active site of the crystal structure of a OP- inhibited AChE.

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We earlier reported an in silico pharmacophore model for reactivation of oximes to tabun-inhibited AChE. Since DFP (diisopropylfluorophosphate) like tabun is a G-agent simulator, we utilized the model as a rational strategy to discover non-oxime reactivators of DFP-inhibited AChE in this study. The phramacophore was used for virtual screening of two commercial databases, Maybridge and ChemNavigator, to identify reactivators which lack the oxime functions.

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