Publications by authors named "D Y Min"

972 Publications

Patient-derived organoids as a preclinical platform for precision medicine in colorectal cancer.

Mol Oncol 2021 Nov 30. Epub 2021 Nov 30.

Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.

Patient-derived organoids are being considered as models that can help guide personalized therapy through in vitro anti-cancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole-exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an "organoid score" based on the variable anti-cancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard-of-care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression-free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA-approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anti-cancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.
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http://dx.doi.org/10.1002/1878-0261.13144DOI Listing
November 2021

Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy.

Biomaterials 2021 Nov 19;280:121257. Epub 2021 Nov 19.

Institute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul, 06683, Republic of Korea. Electronic address:

Recent strategies in cancer immunotherapy based on interleukin-2 (IL-2) are generally focused on reducing regulatory T cell (Treg) development by modifying IL-2 receptor alpha (IL-2Rα) domain. However, the clinical utility of high-dose IL-2 treatment is mainly limited by severe systemic toxicity. We find that peritumorally injectable 'BALLkine-2', recombinant human IL-2 (rIL-2) loaded porous nanoparticle, dramatically reduces systemic side effects of rIL-2 by minimizing systemic IL-2 exposure. Notably, in cynomolgus monkeys, subcutaneous (SC)-injection of BALLkine-2 not only dramatically reduces systemic circulation of rIL-2 in the blood, but also increases half-life of IL-2 compared to IV- or SC-injection of free rIL-2. Peritumorally-injected BALLkine-2 enhances intratumoral lymphocyte infiltration without inducing Treg development and more effectively synergizes with PD-1 blockade than high-dose rIL-2 administration in B16F10 melanoma model. BALLkine-2 could be a highly potent therapeutic option due to higher anti-tumor efficacy with lower and fewer doses and reduced systemic toxicity compared to systemic rIL-2.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121257DOI Listing
November 2021

Controlling pathogenic risks of water treatment biotechnologies at the source by genetic editing means.

Environ Microbiol 2021 Nov 27. Epub 2021 Nov 27.

CAS Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.

Antimicrobial-resistant pathogens in the environment and wastewater treatment systems, many of which are also important pollutant degraders and are difficult to control by traditional disinfection approaches, have become an unprecedented treat to ecological security and human health. Here, we propose the adoption of genetic editing techniques as a highly targeted, efficient and simple tool to control the risks of environmental pathogens at the source. An 'all-in-one' plasmid system was constructed in Aeromonas hydrophila to accurately identify and selectively inactivate multiple key virulence factor genes and antibiotic resistance genes via base editing, enabling significantly suppressed bacterial virulence and resistance without impairing their normal phenotype and pollutant-degradation functions. Its safe application for bioaugmented treatment of synthetic textile wastewater was also demonstrated. This genetic-editing technique may offer a promising solution to control the health risks of environmental microorganisms via targeted gene inactivation, thereby facilitating safer application of water treatment biotechnologies.
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http://dx.doi.org/10.1111/1462-2920.15851DOI Listing
November 2021

Pseudoalteromone A, a Ubiquinone Derivative from Marine spp., Suppresses Melanogenesis.

Mar Drugs 2021 Oct 28;19(11). Epub 2021 Oct 28.

Basic Research & Innovation Division, Amorepacific R&D Unit, Yongin 17074, Korea.

An ubiquinone derivative, pseudoalteromone A (), has been isolated from two marine-derived spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 μg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes.
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http://dx.doi.org/10.3390/md19110612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618130PMC
October 2021

Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice.

Front Neurol 2021 4;12:761912. Epub 2021 Nov 4.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.

Sudden unexpected death in epilepsy (SUDEP) is a fatal event that ranks second in years of potential life lost among neurological disorders. Seizure-induced respiratory arrest (S-IRA) is the primary instigator leading to death in many SUDEP cases. However, there are currently no effective preventive strategies against S-IRA other than the seizure control. Therefore, it is critical to develop new avenues to prevent SUDEP by investigating the pharmacological interventions of S-IRA. In the present study, we examined the effect of genistein, an isoflavone found in various dietary vegetables, on the incidence of S-IRA in DBA/1 mice. DBA/1 mice exhibited generalized seizures and S-IRA when subjected to acoustic stimulation. Genistein was intraperitoneally administered alone or in combination with an adrenoceptor antagonist and a serotonin (5-HT) receptor antagonist, respectively. The effects of drug treatments on S-IRA incidence and seizure behaviors were examined. The incidence of S-IRA in DBA/1 mice was significantly reduced 2 h after injection of genistein at 1-90 mg/kg as compared with that in the vehicle control. Genistein could block S-IRA without interfering with any component of seizures, especially at relatively lower dosages. The S-IRA-suppressing effect of genistein was reversed by an α2 adrenoceptor antagonist but was not altered by an α1 antagonist. The inhibitory effect of genistein on S-IRA was not affected by a 5-HT or 5-HT receptor antagonist. Our data show that genistein reduces S-IRA incidence and can specifically block S-IRA in DBA/1 mice. Its suppressing effect on S-IRA is dependent on activating α2 adrenoceptors. Our study suggests that genistein, a dietary supplement, is potentially useful to prevent SUDEP in at-risk patients.
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http://dx.doi.org/10.3389/fneur.2021.761912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599950PMC
November 2021
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