• Current Optics and Photonics
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• 제4권1호
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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.

• 대한수의학회지
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• 제56권3호
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• pp.177-181
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• 2016

Mini-pigs have been widely employed in preclinical studies to explore new therapeutic strategies for diseases of the human urinary system; however, the normal reference of the renal artery has not been clearly investigated in the mini-pig model. Therefore, we aimed to establish a normal reference of the radiological morphology of the renal artery in mini-pigs by renal angiography via catheterization of the carotid artery. The renal angiographies obtained from 15 mini-pigs were evaluated to determine the orifice from the aorta, facing direction, size and the number of branches of renal arteries. Cranio-laterally facing renal arteries with 2 distal branches were mainly observed in the renal artery of mini-pigs. Both sides of the renal artery presented symmetrical sizes; however, the right renal artery orifice from the aorta was located more cranially than the left counterpart. The results of this study will contribute to radiological diagnosis of the renal artery as well as preclinical studies of mini-pigs.

• Current Optics and Photonics
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• 제3권1호
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• pp.54-65
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• 2019

To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.

• Journal of Medicine and Life Science
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• 제15권2호
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• pp.42-45
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• 2018

Colorectal cancer (CRC) is a third leading cause of cancer-related death in cancer patients. Sporadic and inflammation-related colon carcinogenesis are major mechanism of colorectal cancer. In vivo CRC models have been developed and implicated to understand their mechanisms upon a different type of CRC. Moreover, recently animal models have played important roles in chemopreventive and preclinical trials over the years. In this mini-review, the aim is to introduce various animal models of CRC and help the understanding to establish in vivo experimental plans according to the cancer type of CRC.

• 한국수정란이식학회지
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• 제31권1호
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• pp.97-107
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• 2016

Although many diseases could be treated by the development of modern medicine, there are some incurable diseases including brain cancer, Alzheimer disease, etc. To study human brain cancer, various animal models were reported. Among these animal models, mouse models are valuable tools for understanding brain cancer characteristics. In spite of many mouse brain cancer models, it has been difficult to find a new target molecule for the treatment of brain cancer. One of the reasons is absence of large animal model which makes conducting preclinical trials. In this article, we review a recent study of molecular characteristics of human brain cancer, their genetic mutation and comparative analysis of the mouse brain cancer model. Finally, we suggest the need for development of large animal models using somatic cell nuclear transfer in translational research.

• IMMUNE NETWORK
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• 제15권2호
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• pp.83-90
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• 2015

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

• Journal of Periodontal and Implant Science
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• 제53권1호
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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.

• Journal of Medicine and Life Science
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• 제16권3호
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• pp.55-59
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• 2019

Cerebral vessels are functionally and structurally specialized to provide adequate blood flow to brain which shows high metabolic rates. Cerebral hemorrhage or ischemic infarction due to cerebrovascular injury or occlusion can cause the immediate brain damage, and if not treated rapidly, can lead to serious or permanent brain damages, and sometimes life-threatening. Unlike these popular cerebrovascular diseases, there are diseases caused by genetic problems. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of them. CADASIL does not show the high incidence, but it is considered to be significantly affected by regional obstructiveness such as islands and therefore, to be an important genetic disease in Jeju. This paper aims to summarize the possibility of animal model research that can provide preclinical data for CADASIL disease research and to evaluate its applicability in future research plans.

• Toxicological Research
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• 제30권1호
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• pp.1-5
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• 2014

Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced.

• Journal of Gastric Cancer
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• 제20권1호
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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.