Publications by authors named "KyuKwang Kim"

Ovarian cancer is the leading cause of death among gynecologic malignancies. Despite recent advancements in targeted therapies such as PARP inhibitors, recurrence is common and frequently resistant to existing therapies. A powerful diagnostic tool, coupled with a comprehensive understanding of its implications, is crucial.

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Circulating Tumor Cells (CTCs) may serve as a non-invasive source of tumor material to investigate an individual's disease in real-time. The Parsortix PC1 System, the first FDA-cleared medical device for the capture and harvest of CTCs from peripheral blood of metastatic breast cancer (MBC) patients for use in subsequent user-validated downstream analyses, enables the epitope-independent capture of CTCs with diverse phenotypes based on cell size and deformability. The aim of this study was to determine the proportion of MBC patients and self-declared female healthy volunteers (HVs) that had CTCs identified using immunofluorescence (IF) or Wright-Giemsa (WG) staining.

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Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined.

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Introduction: The Parsortix PC1 system, Food and Drug Administration (FDA) cleared for use in metastatic breast cancer (MBC) patients, is an epitope-independent microfluidic device for the capture and harvest of circulating tumor cells from whole blood based on cell size and deformability. This report details the analytical characterization of linearity, detection limit, precision, and reproducibility for this device.

Methods: System performance was determined using K-EDTA blood samples collected from self-declared healthy female volunteers (HVs) and MBC patients spiked with prelabeled cultured breast cancer cell lines (SKBR3, MCF7, or Hs578T).

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The regulatory effect of non-coding large-scale structural variations (SVs) on proto-oncogene activation remains unclear. This study investigated SV-mediated gene dysregulation by profiling 3D cancer genome maps from 40 patients with colorectal cancer (CRC). We developed a machine learning-based method for spatial characterization of the altered 3D cancer genome.

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Inter-chromosomal interactions play a crucial role in genome organization, yet the organizational principles remain elusive. Here, we introduce a novel computational method to systematically characterize inter-chromosomal interactions using in situ Hi-C results from various cell types. Our method successfully identifies two apparently hub-like inter-chromosomal contacts associated with nuclear speckles and nucleoli, respectively.

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Genetic differences inferred from sequencing reads can be used for demultiplexing of pooled single-cell RNA-seq (scRNA-seq) data across multiple donors without WGS-based reference genotypes. However, such methods could not be directly applied to single-cell ATAC-seq (scATAC-seq) data owing to the lower read coverage for each variant compared to scRNA-seq. We propose a new software, scATAC-seq Variant-based EstimatioN for GEnotype ReSolving (scAVENGERS), which resolves this issue by calling more individual-specific germline variants and using an optimized mixture model for the scATAC-seq.

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Article Synopsis
  • Hi-C and capture Hi-C have improved our understanding of chromatin structure, but there is a need for better computational methods to handle various Hi-C protocols and eliminate biases.
  • A new R package called "covNorm" has been developed to streamline data processing for Hi-C, incorporating normalization, background removal, and detection of significant interactions.
  • CovNorm has shown better or similar reproducibility in analysis, making it a robust tool for normalizing Hi-C data and detecting long-range chromatin contacts, available for free on GitHub.
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  • The mammalian genome's organization within the nucleus has been significantly clarified by Hi-C technology, enhancing our understanding of the 3D chromatin structure.
  • Recent advancements have allowed Hi-C to address complex genome analysis challenges like genome assembly and structural variation detection, particularly in cancer genomics.
  • The review also highlights new bioinformatics tools that leverage Hi-C for studying genomic rearrangements and the potential of single-cell Hi-C to explore cancer genome heterogeneity.
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Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure.

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Article Synopsis
  • Chromosomes in the nucleus are made of DNA and proteins, and their genetic information is encoded in linear sequences that require a 3D understanding for accurate interpretation.
  • Recent advancements in technology have revealed how the 3D structure of the genome is organized and its significance for biological functions.
  • Large-scale genomic variations can disrupt this chromatin structure, influencing gene regulation linked to various diseases, which is the focus of recent research on structural variations.
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Mosquito control is important as mosquitoes are extremely harmful pests that spread various infectious diseases. In this research, we present the preliminary results of an automated system that detects the presence of mosquitoes via image processing using multiple deep learning networks. The Fully Convolutional Network (FCN) and neural network-based regression demonstrated an accuracy of 84%.

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  • Epithelial Ovarian Cancer (EOC) has low survival rates because patients are often diagnosed late and resist standard treatments, highlighting the need for new therapies.
  • Septin-2, a GTP binding protein, has been identified for the first time in EOC and shows overexpression in certain cancerous tissues compared to non-cancerous ones.
  • Knocking down septin-2 in ovarian cancer cells reduced their growth and revealed changes in crucial metabolic pathways, indicating that septin-2 could significantly influence cancer development through its impact on protein modifications and metabolism.
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  • The study investigates Human epididymis secretory protein 4 (HE4) and its role in immune evasion in ovarian cancer, highlighting its selective overexpression as a biomarker for tumorigenesis.
  • Researchers found that HE4 significantly upregulates the gene Dual specificity phosphatase 6 (DUSP6) in immune cells, specifically CD8 and CD56 cells, which leads to reduced phosphorylation of Erk1/2, impacting immune response.
  • The results showed that HE4 increases cancer cell proliferation by impairing the function of critical immune cells, an effect that can be partially reversed using a DUSP6 inhibitor, indicating a potential pathway for therapeutic intervention.
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  • MineLoC is a new tool that uses Minecraft to create 3D printable models for Lab-on-a-Chip devices by allowing users to draw simple diagrams that translate into game blocks.
  • Users can collaboratively edit and review the designs in real-time, which is a unique feature compared to traditional software.
  • The method has proven effective, achieving 86% accuracy in replicating a previous device, and aims to increase accessibility to 3D printing in Lab-on-a-Chip research.
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Microfluidic devices are an emerging platform for a variety of experiments involving bacterial cell culture, and has advantages including cost and convenience. One inevitable step during bacterial cell culture is the measurement of cell concentration in the channel. The optical density measurement technique is generally used for bacterial growth estimation, but it is not applicable to microfluidic devices due to the small sample volumes in microfluidics.

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  • A new method for measuring bacterial growth using an LED array as a marker is proposed, which can be automated and is less affected by external light conditions.
  • This modified approach improves upon the existing marker-based methods that rely on light and image processing, which can be disrupted by background colors or lighting.
  • By using LEDs, the system can work effectively in darkly colored broth and serves as an indicator for regions of interest in images, promising more reliable growth detection.
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The detection of bacterial growth in liquid media is an essential process in determining antibiotic susceptibility or the level of bacterial presence for clinical or research purposes. We have developed a system, which enables simplified and automated detection using a camera and a striped pattern marker. The quantification of bacterial growth is possible as the bacterial growth in the culturing vessel blurs the marker image, which is placed on the back of the vessel, and the blurring results in a decrease in the high-frequency spectrum region of the marker image.

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In this research an open source, low power sensor node was developed to check the growth of mycobacteria in a culture bottle with a nitrate reductase assay method for a drug susceptibility test. The sensor system reports the temperature and color sensor output frequency change of the culture bottle when the device is triggered. After the culture process is finished, a nitrite ion detecting solution based on a commercial nitrite ion detection kit is injected into the culture bottle by a syringe pump to check bacterial growth by the formation of a pigment by the reaction between the solution and the color sensor.

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A sensor node for sampling water and checking for the presence of harmful bacteria such as E. coli in water sources was developed in this research. A chromogenic enzyme substrate assay method was used to easily detect coliform bacteria by monitoring the color change of the sampled water mixed with a reagent.

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Article Synopsis
  • Antiestrogens like tamoxifen and fulvestrant are being studied for treating platinum-resistant ovarian cancer, with human epididymis protein 4 (HE4) being a key factor due to its correlation with platinum resistance.
  • HE4 was observed to translocate to the nucleus in response to hormones and was found to induce resistance to antiestrogens by interacting with estrogen receptor-α (ER-α), leading to ER-α downregulation.
  • The research identified importin-4 as a novel facilitator of HE4’s nuclear transport, revealing that using ivermectin, an importin inhibitor, can enhance the effectiveness of antiestrogen treatments in HE4-overexpressing ovarian cancer cells.
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Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates.

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  • The study explores the potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) as a treatment for advanced endometrial cancer, highlighting the need for new therapies.
  • 7Me-IEITC was found to significantly reduce the viability of endometrial cancer cell lines (ECC-1 and KLE) through mechanisms involving apoptosis and mitochondrial dysfunction.
  • The compound's effect was linked to oxidative stress and specific changes in protein expression, indicating its cytotoxicity may be primarily due to ROS production, suggesting further research is warranted.
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  • Medulloblastoma is the most common brain tumor in children, and researchers are exploring new treatment options using nifurtimox and tetrathiomolybdate (TM) which both increase reactive oxygen species (ROS) levels in cells.
  • The combination of nifurtimox and TM was found to synergistically reduce cell viability and induce apoptosis in medulloblastoma cell lines, confirmed through various analyses including Western blotting and transcriptional profiling.
  • The study suggests that this drug combination enhances oxidative stress and activates apoptosis-related pathways, indicating potential for further investigation as a treatment for medulloblastoma.
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