• Korean Journal of Head & Neck Oncology
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• v.38 no.1
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• pp.1-9
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• 2022

Thyroid cancer is one of the slow-growing tumors with excellent oncological outcomes. However, a small set of patients with unexpectedly severe outcomes are usually ignored. Anaplastic thyroid cancer (ATC) remains one of the most aggressive and lethal solid tumors. Recently, dabrafenib and trametinib combination therapy or neoadjuvant BRAF induction therapy has shown promising results. In addition, a combination of targeted drugs, immunotherapy, surgery, and radiation therapy can improve overall survival in ATC patients. Another disease for which there is no breakthrough treatment is radioactive iodine-refractory differentiated thyroid cancer (DTC). To date, multikinase inhibitors (sorafenib, lenvatinib) targeting the growth factor signaling pathway have been developed and approved as anticancer agents for patients with advanced DTC. This review includes results from multikinase inhibitors to the emergence of new target molecules, including rearrangements during transformation (RET) and tropomyosin receptor kinase (TRK).

• Molecules and Cells
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• v.28 no.5
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• pp.447-453
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• 2009

The quorum sensing (QS) inhibitors that antagonize TraR, a receptor protein for N-3-oxo-octanoyl-L-homoserine lactones (3-oxo-C8-HSL), a QS signal of Agrobacterium tumefaciens were developed. The structural analogues of 3-oxo-C8-HSL were designed by in silico molecular modeling using SYBYL packages, and synthesized by the solid phase organic synthesis (SPOS) method, where the carboxamide bond of 3-oxo-C8-HSL was replaced with a nicotinamide or a sulfonamide bond to make derivatives of N-nicotinyl-L-homoserine lactones or N-sulfonyl-L-homoserine lactones. The in vivo inhibitory activities of these compounds against QS signaling were assayed using reporter systems and compared with the estimated binding energies from the modeling study. This comparison showed fairly good correlation, suggesting that the in silico interpretation of ligand-receptor structures can be a valuable tool for the pre-design of better competitive inhibitors. In addition, these inhibitors also showed anti-biofilm activities against Pseudomonas aeruginosa.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.231-237
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• 2006

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Histocultures are in vitro 3 dimensional cultures of tumor tissues and maintain the characteristic microenvironment of human solid tumors in vivo including hypoxia and multicellular structure. In this study, we evaluated the pharmacodynamics of tirapazamine(TPZ), a hypoxia-selective cytotoxin, in human non small cell lung cancer(NSCLC) cells grown as monolayers and histocultures. Antiproliferative activity of TPZ was determined after various conditions of drug exposure, and cell cycle arrest and apoptosis were also measured using flow cytometry. In monolayers, hypoxia selectivity measured by hypoxic/normoxic cytotoxicity ratio was increased with longer exposure. Lower cytotoxicity of TPZ was observed in histocultures compared to monolayers, however, a similar level of cytotoxicity was obtained with longer exposure of 96 hr. TPZ induced $G_2/M$ arrest and apoptosis in both culture conditions, which were greatly enhanced under hypoxic condition. Our data clearly showed the different pharmacodynamics of TPZ in monolayers and histocultures. Antiproliferative activity of TPZ against human solid tumors can be improved with longer drug exposure by exploiting drug delivery systems or by combining angiogenesis inhibitors to maintain drug concentration in tumor tissues.

• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.381-386
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• 2011

Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

• Journal of Microbiology and Biotechnology
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• v.22 no.3
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• pp.339-342
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• 2012

This study describes the characterization of a new angiotensin I-converting enzyme (ACE) inhibitory peptide from a Korean traditional rice wine. After purification of the ACE inhibitor peptides with ultrafiltration, Sephadex G-25 column chromatography, and successively $C_{18}$ and SCX solid-phase extraction, reverse-phase HPLC, and size exculsion chromatography, two types of the purified ACE inhibitors with $IC_{50}$ values of 0.34 mg/ml and 1.23 mg/ml were finally obtained. The two purified ACE inhibitors (F-1 and F-2) were found to have two kinds of novel oligopeptides, showing very little similarity to other ACE inhibitory peptide sequences. The amino acid sequences of the two purified oligopeptides were found to be Gln-Phe-Tyr-Ala-Val (F-1) and Ala-Gly-Pro-Val-Leu-Leu (F-2), and their molecular masses were estimated to be 468.7 Da (F-1) and 357.7 Da (F-2), respectively. They all showed a clear antihypertensive effect on spontaneously hypertensive rats at a dosage of 500 mg/kg.

• Journal of the Korean Ceramic Society
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• v.53 no.5
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• pp.494-499
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• 2016

In this work, the effects of different sintering inhibitors added to $La_{0.8}Sr_{0.2}MnO_{3-{\partial}}$ (LSM) were studied to obtain an optimum cathode material for cathode-supported type of Solid oxide fuel cell (SOFC) in terms of phase stability, mechanical strength, electric conductivity and porosity. Four different sintering inhibitors of $Al_2O_3$, $CeO_2$, NiO and gadolinium doped ceria (GDC) were mixed with LSM powder, sintered at $1300^{\circ}C$ and then they were evaluated. The phase stability, sintering behavior, electrical conductivity, mechanical strength and microstructure were evaluated in order to assess the performance of the mixture powder as cathode support material. It has been found that the addition of $Al_2O_3$ undesirably decreased the electrical conductivity of LSM; other sintering inhibitors, however, showed sufficient levels of electrical conductivity. GDC and NiO addition showed a promising increase in mechanical strength of the LSM material, which is one of the basic requirements in cathode-supported designs of fuel cells. However, NiO showed a high reactivity with LSM during high temperature ($1300^{\circ}C$) sintering. So, this study concluded that GDC is a potential candidate for use as a sintering inhibitor for high temperature sintering of cathode materials.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.93.1-93.11
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• 2018

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

• Journal of Korean Society on Water Environment
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• v.27 no.6
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• pp.769-775
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• 2011

An experimental study of biofilm nitritation system for high-strength ammonium wastewater has been carried out to examine the temperature effect on different organic and solid concentration. Operating temperature varied from $35^{\circ}C$ to $15^{\circ}C$. The influent N concentration of identical three reactors was adjusted to about $300mg\;NH_4-N/L$. A control unit fed with a synthetic wastewater, while the others were fed with reject water which is consisted of the supernatant of both digester and thickener. The results indicated that nitrite accumulation was stable in temperature range of $35^{\circ}C$ to $25^{\circ}C$. However, nitritation was significantly reduced at below $20^{\circ}C$. Free ammonia (FA) and free nitrous acid (FNA) were major inhibitors to the nitrite oxidizer for nitrite accumulation in lower temperature. From the estimation of temperature coefficient (${\Theta}$) of biofilm and suspended nitritation system, biofilm nitritation system could absorb the negative temperature effect compared with suspended nitritation system.

• Journal of Microbiology and Biotechnology
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• v.19 no.4
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• pp.368-371
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• 2009

In the course of screening for the melanogenesis inhibitors, aspochalasin I was isolated from solid-state culture of Aspergillus sp. Fb020460. Its structure was determined by spectroscopic analysis including mass spectroscopy and NMR analysis. Aspochalasin I potently inhibited melanogenesis in Mel-Ab cells with an $IC_{50}$ value of $22.4{\mu}M$ without cytotoxicity.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.3004-3008
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• 2012

Small molecule conjugated peptides were prepared by solid-phase synthesis as potential novel whitening agents, and their melanogenesis inhibitory activities were investigated. The conjugated small molecules were well-known materials as tyrosinase inhibitors, and peptides were selected from the sequences that are known to antagonize melanocortin receptor 1 (MC1R). Most of small molecules-peptide conjugates showed superior melanin inhibition activity to kojic acid and arbutin. Among these, almost all compounds have -AR- sequence. From this study, we concluded that the small molecule conjugated peptides containing -AR- sequence have melanogenesis inhibitory activities and have potential to be used as novel whitening agents.