• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.135-140
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• 1994

Over past decades, numerous in vitro model has been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as : 1. the characterization of main biotransformation reactions. 2. the identification of phase I and phase II isozymes involved in such reactions 3. the evaluation of interspecies differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles 4. the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions 5. the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obstained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.58-65
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• 2015

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

• Journal of Life Science
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• v.32 no.8
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• pp.611-621
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• 2022

Dimethyl sulfoxide (DMSO) is commonly used as control or vehicle solvent in preclinical research of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) due to its ability to dissolve lipophilic compounds and cross the blood brain barrier. However, the biochemical effects of DMSO on the outcomes of preclinical research are often overlooked. In the present study, we investigated whether the long-term oral administration of 5% DMSO affects the neurological, functional, and histological disease phenotype of the copper/zinc superoxide dismutase glycine 93 to alanine mutation (SOD1-G93A) mouse model of amyotrophic lateral sclerosis. SOD1-G93A transgenic mice showed shortened survival time and reduced motor function. We found that administration with DMSO led to increased mean survival time, reduced neurological scores, and improved motor performance tested using the rotarod and grip strength tests. On the other hand, DMSO treatment did not attenuate motor neuron loss in the spinal cord and denervation of neuromuscular junctions in the skeletal muscle. These results suggest that DMSO administration could improve the quality of life of the SOD1-G93A mouse model of ALS without affecting motor neuron denervation. In conclusion, the use of DMSO as control or vehicle solvent in preclinical research may affect the behavioral outcomes in the SOD1-G93A mouse model. The effect of the vehicle should be thoroughly considered when interpreting therapeutic efficacy of candidate drugs in preclinical research.

• Journal of Preventive Medicine and Public Health
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• v.57 no.3
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• pp.252-259
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• 2024

Objectives: This study investigated factors associated with the retention of people living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) during the first 3 years of treatment. Methods: A retrospective study using electronic health records was conducted at a tertiary hospital in Jakarta, Indonesia. Adult HIV-positive patients who started ART from 2010 until 2020 were included. A binary logistic regression model was used to identify factors associated with ART retention in the first 3 years. Results: In total, 535 respondents were included in the analysis. The ART retention rates for the first, second, and third years were 83.7%, 79.1%, and 77.2%, respectively. The multivariate analysis revealed a negative association between CD4 count when starting ART and retention. Patients with CD4 counts >200 cells/mL were 0.65 times less likely to have good retention than those with CD4 counts ≤200 cells/mL. The year of starting ART was also significantly associated with retention. Patients who started ART in 2010-2013 or 2014-2016 were less likely to have good retention than those who started ART in 2017-2020, with adjusted odds ratios of 0.52 and 0.40, respectively. Patients who received efavirenz-based therapy were 1.69 times more likely to have good retention than those who received nevirapine (95% confidence interval, 1.05 to 2.72). Conclusions: Our study revealed a decline in ART retention in the third year. The CD4 count, year of enrollment, and an efavirenz-based regimen were significantly associated with retention. Patient engagement has long been a priority in HIV programs, with interventions being implemented to address this issue.

• Korean Journal of Oriental Medicine
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• v.1 no.1
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• pp.69-99
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• 1995

In order to develop experimental research in oriental medicine, it is necessary to make experimental model of diagnostic pattern(證), On model of the condition of a disease maked in china, there are cold-pattern(寒證), heat-pattern(熱證), deficiency of vital energy-pattern(氣虛證), blood-deficiency-pattern(血虛證), yin-deficiency-pattern(陰虛證), yang-deficiency-pattern(陽虛證), deficiency of both yin and yang-pattern(陰陽俱虛證), yang-exhaustion-pattern(亡陽證), blood stasis-pattern(血瘀證), pattern of defferential diagnosis according to states of viscera(臟腑辨證).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.63-68
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• 2013

Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.

• Korean Journal of Biological Psychiatry
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• v.10 no.1
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• pp.20-44
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• 2003

Schizophrenics suffer not only psychotic symptoms but also cognitive deficits such as an attentional difficulty, memory impairment, poor abstraction, etc. These cognitive abnormalities have been reported to be significantly related to the social and occupational outcome in schizophrenia. Thus, it is important to explore the cause and pathophysiology for the cognitive abnormalities in patients with schizophrenia. In this regard, hippocampus is one of the most promising brain areas to search for the clue because it is closely involved in memory related function. In fact, during the past several decades, there have been extensive studies supporting hippocampal abnormalities as a cause of schizophrenia in both clinical and preclinical field. In this review, basic anatomical knowledge about hippocampus and major findings of preclinical and clinical studies which investigated the correlation between schizophrenia and hippocampus were highlighted. The contents are 1) anatomical structure of hippocampus, 2) neuronal pathway and receptor distribution in hippocampus, 3) function of hippocampus, 4) hippocampal animal model for schizophrenia, 5) hippocampus-related studies on antipsychotic drugs, and 6) clinical studies in hippocampus in patients with schizophrenia.

• Journal of mucopolysaccharidosis and rare diseases
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• v.5 no.1
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• pp.39-41
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• 2021

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder of hyperphagia leading to severe obesity, intellectual deficits, compulsivity, and other behavioral problems. PWS is caused by the inactivation of contiguous genes on chromosome 15q11-q13, which complicates the development of targeted, effective therapeutics. Various preclinical studies have been conducted by developing mouse models that exhibit phenotypes similar to PWS. Oxytocin deficiency in PWS is associated with hyperphagia with impaired satiety and, food-seeking and behavior disorders. Here, we summarize the oxytocin study of ingestion behavior tested in the PWS mouse model and published data from clinical trials that have evaluated treatment effectiveness on ingestion behavior and social dysfunction in patients with PWS.

• Journal of Korean Neurosurgical Society
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• v.61 no.5
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• pp.539-547
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• 2018

Traumatic spinal cord injury (SCI) research has recently focused on the use of rat and mouse models for in vivo SCI experiments. Such small rodent SCI models are invaluable for the field, and much has been discovered about the biologic and physiologic aspects of SCI from these models. It has been difficult, however, to reproduce the efficacy of treatments found to produce neurologic benefits in rodent SCI models when these treatments are tested in human clinical trials. A large animal model may have advantages for translational research where anatomical, physiological, or genetic similarities to humans may be more relevant for pre-clinically evaluating novel therapies. Here, we review the work carried out at the University of British Columbia (UBC) on a large animal model of SCI that utilizes Yucatan miniature pigs. The UBC porcine model of SCI may be a useful intermediary in the pre-clinical testing of novel pharmacological treatments, cell-based therapies, and the "bedside back to bench" translation of human clinical observations, which require preclinical testing in an applicable animal model.

• Current Optics and Photonics
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• v.4 no.1
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• pp.57-62
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• 2020

The selection of anesthetic agent is important in preclinical studies, since each agent affects the systemic hemodynamics in different ways. For that reason, we hypothesized that different anesthetic agents will result in different vaginal hemodynamic response and temperature during sexual arousal, in an animal model. To validate the hypothesis, animal experiments were performed using female rats with two anesthetic agents widely used in preclinical studies: ketamine and isoflurane. Our previously developed near-infrared-spectroscopy-based probe was used to measure the changes of oxyhemoglobin (OHb), deoxyhemoglobin (RHb), and total hemoglobin (THb) concentrations along with temperature from the animal vaginal wall. As a control, saline was administered to both isoflurane- and ketamine-anesthetized animals, and did not show any significant changes in OHb, RHb, THb, or temperature. However, an administration of apomorphine (APO, 80 ㎍/kg) induced increases of OHb (63 ± 28 μM/DPF), RHb (35 ± 20 μM/DPF), and THb (98 ± 49 μM/DPF) in ketamine-anesthetized animals, while decreases of OHb (52 ± 76 μM/DPF) and THb (38 ± 30 μM/DPF) and an increase of RHb (28 ± 51 μM/DPF) were found in isoflurane-anesthetized animals. The vaginal temperature decreased from the baseline in both ketamine-(0.42℃) and isoflurane-(1.22℃)anesthetized animals. These results confirmed our hypothesis, and suggest that a preclinical study monitoring hemodynamic responses under anesthesia should employ an appropriate anesthetic agent for the study.