• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2287-2290
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• 2014

Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.23 no.1
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• pp.1-10
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• 2013

Objectives: The present study investigated the potential subacute toxicity of 1,4-dichlorobutane (1,4-DCB) by a 2-week repeated oral dose in male Sprague-Dawley rats. Materials and Methods: The test chemical was administered once daily by gavage to male rats at dose levels of 0, 74, 222, 667, and 2000 mg/kg/day for 2 weeks. All rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food and water consumption, urinalysis, hematology, serum biochemistry, gross findings, and organ weights were examined. Results: At 2000 mg/kg/day, treatment-related clinical signs, as evidenced by hypothermia, decreased locomotor activity, piloerection, lying on side, and prone position were observed. All the rats were found dead on test day 2. At 667 mg/kg/day, polyuria, suppressed body weight gain, food consumption, and spleen and thymus weights, and increased adrenal gland and liver weights were observed.Hematological and serum biochemical investigations revealed increases in the alanine aminotransferase, alkaline phosphataseand total bilirubinand decreases in the serum $Na^+$ level, white blood cell count and lymphocyte ratio. There were no treatment-related adverse effects in the 74 and 222 mg/kg/day groups. Conclusions: In the present experimental conditions, target organs were determined to be spleen, thymus,and liver. The no-observed-adverse-effect level was considered to be 222 mg/kg/day in male rats.

• Journal of Oriental Neuropsychiatry
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• v.32 no.2
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• pp.95-109
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• 2021

Objectives: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Mental sequelae occurring in patients with COVID-19 and the general population are important concerns. In Korea, herbal medicine is used nationwide to respond to this pandemic. It can be prescribed by COVID-19 telemedicine center of Korean medicine (KM). Among some herbal medicines, Gamiguibi-tang is the only herbal medicine prescribed for individuals with mental health, especially for those with insomnia. In this mini-review, the objective of this study was to summarize the evidence of some promising herbal medicines available for treating primary insomnia based on existing clinical and preclinical studies. Methods: A research team was formed for KM clinical practice guidelines for insomnia (version 1.0). Team members were provided with a list of references of relevant herbal medicines for insomnia. To gather evidence from clinical studies with appropriate sample sizes, among the list of references, randomized controlled trials for primary insomnia that included 50 subjects or more per arm and used herbal medicine were included in the final analysis. Moreover, pre-clinical studies examining the mechanism of action of each herbal medicine and studies on herb-drug interactions, were searched and summarized. Results: Four herbal medicines (Ondam-tang, Sanjoin-tang, Guibi-tang, and Hyeolbuchugeo-tang) were reviewed based on existing clinical and preclinical studies. Based on findings of existing studies, some suggestions of herbal medicines for insomnia in the COVID-19 era in Korea were suggested. Conclusions: Data of this study could be used to prepare a future revision of the manual of COVID-19 telemedicine center of KM.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.93-98
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• 2021

meta-iodobenzylguanidine is one of the norepinephrine analogs and reuptakes together with norepinephrine with norepinephrine transporter. The radioiodinated ligand, ¹²³I-meta-iodobenzylguanidine, is the most widely used for single photon emission computed tomography imaging to diagnose functional abnormalities and tumors of the sympathetic nervous system. In this study, we performed cellular uptake studies of ¹²³I-meta-iodobenzylguanidine in positive- and negative-norepinephrine transporter cells in vitro to verify the uptake activity for norepinephrine transporter. After ¹²³I-meta-iodobenzylguanidine was injected via a tail vein into normal mice, Single photon emission computed tomography/computed tomography images were acquired at 1 h, 4 h, and 24 h post-injection, and quantified the distribution in each organ including the adrenal medulla as a norepinephrine transporter expressing organ. In vitro cell study showed that ¹²³I-meta-iodobenzylguanidine specifically uptaked via norepinephrine transporter, and significant uptake of ¹²³I-meta-iodobenzylguanidine in the adrenal medulla in vivo single photon emission computed tomography images. These results demonstrated that single photon emission computed tomography imaging with ¹²³I-meta-iodobenzylguanidine were able to quantify the biodistribution in vivo in the adrenal medulla in normal mice.

• Journal of Periodontal and Implant Science
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• v.53 no.1
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• pp.20-37
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• 2023

Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2863-2868
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• 2014

Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigated for association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aim of this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene for GC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10, 2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874 cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated that the variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG (odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18, and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07, 95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysis by Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58, 95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions: This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GC in Asians and Indians.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

• Journal of the Korean Society of Radiology
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• v.17 no.1
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• pp.11-16
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• 2023

In preclinical positron emisson tomography(PET), spatial resolution degradation occurs outside the field of view(FOV). To solve this problem, a depth of interaction(DOI) detector was developed that measures the position where gamma rays and the scintillator interact. There are a method in which a scintillation pixel array is composed of multiple layers, a method in which photosensors are arranged at both ends of a single layer, a method in which a scintillation pixel array is constituted in several layers and a photosensor is arranged in each layer. In this study, a new type of DOI detector was designed by analyzing the characteristics of the previously developed detectors. In the two-layer detector, different sizes of scintillation pixels were used for each layer, and the array size was configured differently. When configured in this form, the positions of the scintillation pixels for each layer are arranged to be shifted from each other, so that they are imaged at different positions in a flood image. DETECT2000 simulation was performed to confirm the possibility of measuring the depth of interaction of the designed detector. A flood image was reconstructed from a light signal acquired by a gamma-ray event generated at the center of each scintillation pixel. As a result, it was confirmed that all scintillation pixels for each layer were separated from the reconstructed flood image and imaged to measure the interaction depth. When this detector is applied to preclinical PET, it is considered that excellent images can be obtained by improving spatial resolution.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.249-255
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• 2022

Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.14 no.1
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• pp.151-166
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• 2019

New drug development requires 10 to 15 years of long time and more than $ 1 billion in funding, ranging from basic research${\rightarrow}$preclinical medicine${\rightarrow}$clinical medicine${\rightarrow}$product approval${\rightarrow}$sales. Many new drug development bio-venture companies will continue to pursue new drug development with funds secured through listing on the securities market. This study focuses on the impact of the listing on the market of bio-venture companies in the development of new drugs. It is necessary to determine whether the increase in registered patent, preclinical, clinical and technology transfer contracts at the time of listing (D) The results of this study are as follows. We also analyzed whether the registered patent, preclinical, and clinical effects had significant effect on technology transfer contracts at two years after listing and listing. The results of the analysis are as follows. First, Korea's new drug development bio-venture firms increased their registered patents but did not increase their pre-clinical, clinical and technology transfer contracts. Second, at the time of listing and two years after listing, pre-employment has a significant effect on Korea's technology transfer contracts and has a significant effect on overseas technology transfer contracts. However, registered patents and clinics have significant influence on technology transfer contracts. Korea 's new drug development bio-venture firms showed patent increase despite the stock market listing, but pre-clinical, clinical and technology transfer contracts did not increase. In order to strengthen technological commercialization of new drug development bio-venture companies in the future, it is required to establish R & D strategy for efficient use of IPO subscription funds, open innovation through strengthening industry-academia-partnerships, and more sophisticated preclinical and clinical strategy establishment.