• Journal of Gastric Cancer
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• v.19 no.4
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• pp.375-392
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• 2019

Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

• Proceedings of the Korean Society of Toxicology Conference
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• 1997.10a
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• pp.38-42
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• 1997

Human growth hormone is known as one of the peptide hormones which is consisted of 191 amino acids derived from the pituitary gland in humans. The objectives of this study were to supply inexpensive recombinant methionyl human growth hormones (rHGH) synthesized by the DNA technology in a yeast cell line and followed by the establishement of protein purification techniques. The next steps of the research were to study its physic-chemical properties and biological properties, and to evaluate various preclinical aspcts including pharmacokinetics sutdy, general pharmacology study, general toxicity test, and specific toxicity tests. Clinical phase I, II, III studies were also done against growth hormone dficient children to reveal that growth promoting effects were similar compared with the natural HGH extracted from pituitary glands and commercially available rHGHs. The results could be summarized that (I) this yeast dervied rHGH have had excellent physico-chemical and biological properties in comparison with a natural HGH and other synthesized rHGHs, (2) we could not see any toxic side effects when very high doses were administered to the experimental animals, and (3) this growth hormone showed effectiveness in the growth stimulating to growth hormone deficient patients.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.10.1-10.11
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• 2018

Although early studies suggested that bladder cancer (BCa) is more prevalent in men than in women, muscle-invasive rates are higher in women than in men, suggesting that sex hormones might play important roles in different stages of BCa progression. In this work, we found that estrogen receptor beta ($ER{\beta}$) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2/DAB2 interacting protein) signals and that blocking miR-92a expression with an inhibitor could partially reverse $ER{\beta}$-enhanced BCa cell growth and invasion. Further mechanism dissection found that $ER{\beta}$ could increase miR-92a expression at the transcriptional level via binding to the estrogen-response-element (ERE) on the 5' promoter region of its host gene C13orf25. The $ER{\beta}$ up-regulated miR-92a could decrease DAB2IP tumor suppressor expression via binding to the miR-92a binding site located on the DAB2IP 3' UTR. Preclinical studies using an in vivo mouse model also confirmed that targeting this newly identified $ER{\beta}$/miR-92a/DAB2IP signal pathway with small molecules could suppress BCa progression. Together, these results might aid in the development of new therapies via targeting of this $ER{\beta}$-mediated signal pathway to better suppress BCa progression.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• Journal of the Korean Society of Radiology
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• v.15 no.5
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• pp.643-647
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• 2021

The purpose of this study was to access the possibility and ideal model for corrosive-induced tissue hyperplasia in the rat esophagus. Twenty rat were divided into two group: a healthy group, corrosive group. corrosive burn in esophagus were produced using 30% NaOH on the distal esophagus. After surgical procedure, behavioral and weight changes were monitored on a weekly. At 3 weeks after surgical procedure, fluoroscopic esophagogram was performed and then all rats sacrificed for histological analysis by administering inhalable pure carbon dioxide. Technical surgery for corrosive stricture were 100%. A total of 2 rats died in corrosive group from a corrosive burn related to dysphagia within 14 days. The esophageal stenosis ratio was significantly higher in the corrosive group than in the healthy group (40.1 ± 9.2 % and 1.4 ± 7.2%, respectively; p = 0.001). The tissue hyperplasia ratio was also significantly higher in the Corrosive group (62.5 ± 9% and 22.08 ± 6%, respectively; p = 0.001). Infusion of 30% NaOH may suggest alternative option to evaluation tool for preclinical study in a rat corrosive model.

• Korean Medical Education Review
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• v.23 no.3
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• pp.185-193
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• 2021

Students must be familiar with clinical skills before starting clinical practice to ensure patients' safety and enable efficient learning. However, performance is mainly tested in the third or fourth years of medical school, and studies using the validity framework have not been reported in Korea. We analyzed the validity of a performance test conducted among second-year students classified into content, response process, internal structure, relationships with other variables, and consequences according to Messick's framework. As results of the analysis, content validity was secured by developing cases according to a pre-determined blueprint. The quality of the response process was controlled by training and calibrating raters. The internal structure showed that (1) reliability by generalizability theory was acceptable (coefficients of 0.724 and 0.786, respectively, for day 1 and day 2), and (2) the relevant domains had proper correlations, while the clinical performance examination (CPX) and objective structured clinical examination (OSCE) showed weaker relationships. OSCE/CPX scores were correlated with other variables, especially grade point average and oral structured exam scores. The consequences of this assessment were (1) making students learn clinical skills and study themselves, while causing too much stress for students due to lack of motivation; (2) reminding educators of the need to apply practical teaching methods and to give feedback on the test results; and (3) providing an opportunity for faculty to consider developing support programs. It is necessary to develop the blueprint more precisely according to students' level and to verify the validity of the response process with statistical methods.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.55-62
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• 2019

HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the $T_{1/2}$ was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice ($19.32{\pm}1.16mg/g$) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.

• Korean Medical Education Review
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• v.21 no.1
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• pp.1-12
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• 2019

This study is a narrative review introducing global trends in patient safety education within medical schools and exploring the status of Korean education. Core competences for patient safety include patient centeredness, teamwork, evidence- and information-based practice, quality improvement, addressing medical errors, managing human factors and system complexity, and patient safety knowledge and responsibility. According to a Korean report addressing the role of doctors, patient safety was described as a subcategory of clinical care. Doctors' roles in patient safety included taking precautions, educating patients about the side effects of drugs, and implementing rapid treatment and appropriate follow-up when patient safety is compromised. The Korean Association of Medical Colleges suggested patient safety competence as one of eight essential human and society-centered learning outcomes. They included appropriate attitude and knowledge, human factors, a systematic approach, teamwork skills, engaging with patients and carers, and dealing with common errors. Four Korean medical schools reported integration of a patient safety course in their preclinical curriculum. Studies have shown that students experience difficulty in reporting medical errors because of hierarchical culture. It seems that patient safety is considered in a narrow sense and its education is limited in Korea. Patient safety is not a topic for dealing with only adverse events, but a science to prevent and detect early system failure. Patient safety emphasizes patient perspectives, so it has a different paradigm of medical ethics and professionalism, which have doctor-centered perspectives. Medical educators in Korea should understand patient safety concepts to implement patient safety curriculum. Further research should be done on communication in hierarchical culture and patient safety education during clerkship.

• The Journal of the Korea institute of electronic communication sciences
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• v.14 no.3
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• pp.619-626
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• 2019

The advances of semiconductor and circuitry technology dovetailed with nano processing techniques have further enhanced micro-miniaturization, sensitivity, longevity and reliability in MID(Medical Implant Device). Nevertheless, one of the remaining challenges is whether power can sufficiently and continuously be supplied for the operation of the MID. Self-powered MID that harvest biomechanical energy from human motion, respiratory and muscle movement are part of a paradigm shift. In this paper, we developed a rechargeable pacemaker through self-power generation with the triboelectric nanogenerator. We demonstrate a fully implanted pacemaker based on an implantable triboelectric nanogenerator, which act as a storage as well as active movement on a large-animal(dog) scale. The self-power pacemaker harvested from animal motion is 2.47V, which is higher than the required pacemaker device sensing voltage(1.35V).