• Title/Summary/Keyword: Preclinical study

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Insulin Resistance Reduces Sensitivity to Cis-Platinum and Promotes Adhesion, Migration and Invasion in HepG2 Cells

  • Li, Lin-Jing;Li, Guang-Di;Wei, Hu-Lai;Chen, Jing;Liu, Yu-Mei;Li, Fei;Xie, Bei;Wang, Bei;Li, Cai-Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3123-3128
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    • 2014
  • The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.

A Numerical Study of Different Types of Collimators for a High-Resolution Preclinical CdTe Pixelated Semiconductor SPECT System

  • Jeong, Hyun-Woo;Kim, Jong Seok;Bae, Se Young;Seo, Kanghyen;Kim, Seung Hun;Kang, Seong Hyeon;Shin, Dong Jin;Lee, Chang-Lae;Kim, Kyuseok;Lee, Youngjin
    • Journal of the Optical Society of Korea
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    • v.20 no.6
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    • pp.663-668
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    • 2016
  • In single-photon-emission computed tomography (SPECT) with a pixelated semiconductor detector (PSD), not only pinhole collimators but also parallel-hole collimators are often used in preclinical nuclear-medicine imaging systems. The purpose of this study was to evaluate and compare pinhole and parallel-hole collimators in a PSD. For that purpose, we paired a PID 350 (Ajat Oy Ltd., Finland) CdTe PSD with each of the four collimators most frequently used in preclinical nuclear medicine: (1) a pinhole collimator, and (2) low-energy high-resolution (LEHR), (3) low-energy general-purpose (LEGP), and (4) low-energy high-sensitivity (LEHS) parallel-hole collimators. The sensitivity and spatial resolution of each collimator was evaluated using a point source and a hot-rod phantom. The highest sensitivity was achieved using LEHS, followed by LEGP, LEHR, and pinhole. Also, at a source-to-collimator distance of 2 cm, the spatial resolution was 1.63, 2.05, 2.79, and 3.45 mm using pinhole, LEHR, LEGP, and LEHS, respectively. The reconstructed hot-rod phantom images showed that the pinhole collimator and the LEHR parallel-hole collimator give a fine spatial resolution for preclinical SPECT with PSD. In conclusion, we successfully compared different types of collimators for a preclinical pixelated semiconductor SPECT system.

The Influence of Circadian Gene Per2 on Cell Damaged by Ultraviolet C

  • Liu, Yanyou;Wang, Yuhui;Jiang, Zhou;Xiao, Jing;Wang, Zhengrong
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.308-314
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    • 2011
  • It has been shown that circadian genes not only play an important role on circadian rhythms, but also participate in other physiological and pathological activities, such as drug dependence, cancer development and radiation injury. The Per2, an indispensable component of the circadian clock, not only modulates circadian oscillations, but also regulates organic function. In the present study, we applied mPER2-upregulated NIH3T3 cells to reveal the relationship of mPer2 and the cells damaged by ultraviolet C (UVC). NIH3T3 cells at the peak of the expression of mPer2 induced by phorbol 12-myristate 13-acetate (PMA) demonstrated little damage by UVC evaluated by MTT assay, cell growth curves and cell colony-forming assay, compared with that at the nadir of the expression of mPer2. Overexpression of mPER2, accompanied p53 upregulated, also demonstrated protective effect on NIH3T3 cells damaged by UVC. These results suggest that mPer2 plays a protective effect on cells damaged by UVC, whose mechanism may be involved in upregulated p53.

Electron beam scattering device for FLASH preclinical studies with 6-MeV LINAC

  • Jeong, Dong Hyeok;Lee, Manwoo;Lim, Heuijin;Kang, Sang Koo;Lee, Sang Jin;Kim, Hee Chang;Lee, Kyohyun;Kim, Seung Heon;Lee, Dong Eun;Jang, Kyoung Won
    • Nuclear Engineering and Technology
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    • v.53 no.4
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    • pp.1289-1296
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    • 2021
  • In this study, an electron-scattering device was fabricated to practically use the ultra-high dose rate electron beams for the FLASH preclinical research in Dongnam Institute of Radiological and Medical Sciences. The Dongnam Institute of Radiological and Medical Sciences has been involved in the investigation of linear accelerators for preclinical research and has recently implemented FLASH electron beams. To determine the geometry of the scattering device for the FLASH preclinical research with a 6-MeV linear accelerator, the Monte Carlo N-particle transport code was exploited. By employing the fabricated scattering device, the off-axis and depth dose distributions were measured with radiochromic films. The generated mean energy of electron beams via the scattering device was 4.3 MeV, and the symmetry and flatness of the off-axis dose distribution were 0.11% and 2.33%, respectively. Finally, the doses per pulse were obtained as a function of the source to surface distance (SSD); the measured dose per pulse varied from 4.0 to 0.2 Gy/pulse at an SSD range of 20-90 cm. At an SSD of 30 cm with a 100-Hz repetition rate, the dose rate was 180 Gy/s, which is sufficient for the preclinical FLASH studies.

Veterinary management protocol for non-human primates: quarantine, anesthesia, and postoperative care for mastoidectomy at animal research institutions

  • Yoon Beom Lee;Woori Jo;Eui-Suk Jeong;Tae Ku Kang;Gwang-Hoon Lee
    • Korean Journal of Veterinary Research
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    • v.63 no.4
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    • pp.35.1-35.10
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    • 2023
  • Non-human primate (NHP) research faces challenges due to zoonosis risk and complex veterinary management yet lacks standardized guidelines for animal care. Therefore, we developed an advanced veterinary management protocol for NHP quarantine, anesthesia, and postoperative care. Three female 4 to 5-year-old cynomolgus monkeys were anesthetized and underwent various tests, including body weight, temperature, blood tests, urinalysis, microbiological monitoring, and physical and dental examinations. Ivermectin and medicated baths were administered to eradicate ectoparasites and endoparasites, and testing was repeated 30 days later. Following quarantine, we performed computed tomography and anesthesia maintenance for mastoidectomy. To relieve pain and maintain body weight, we administered tramadol intramuscularly 4 times/day for 3 days and meloxicam subcutaneously twice daily for 14 days. Feed replacements were provided. During the 33-day quarantine period, physical examinations revealed no abnormalities indicative of infectious diseases, and no specific clinical symptoms were observed. Through a preliminary test of anesthesia time, we selected ketamine 4 mg/kg + medetomidine 50 ㎍/kg for short experiments such as computed tomography, and ketamine 8 mg/kg + medetomidine 50 ㎍/kg for intubation. Ten days after mastoidectomy, NHPs consumed 100 kcal/kg and recovered their body weight. This study offers advanced veterinary management guideline for NHP research. Such protocols can lead to more standardized and ethical practices in NHP research, thereby enhancing the quality of studies on NHPs and the translation of findings to human health and disease.

Factors Associated With Long-term Retention in Antiretroviral Therapy Among People Living With HIV: Evidence From a Tertiary Hospital in Jakarta, Indonesia

  • Ifael Yerosias Mauleti;Krishna Adi Wibisana;Djati Prasetio Syamsuridzal;Sri Mulyati;Vivi Lisdawati;Ika Saptarini;Nurhayati;Armedy Ronny Hasugian;Harimat Hendarwan
    • 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.

The P275A Polymorphism in the Macrophage Scavenger Receptor 1 Gene and Prostate Cancer Risk: a Meta-Analysis

  • Zhou, Qiao-Xia;Tang, Jian-Qiu;Zhao, Fen;Wei, Fu-Lin;Huang, Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5407-5413
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    • 2015
  • Background: Published data regarding associations between the P275A polymorphism in the macrophage scavenger receptor 1 (MSR1) gene and prostate cancer (PCa) risk are inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of P275A polymorphism in MSR1 gene for PCa. Materials and Methods: A systematic literature search was carried out in Pubmed, Medline (Ovid), Embase, CBM, CNKI, Weipu, and Wanfang databases, covering all available publications (last search was performed on Apr 27, 2015). Statistical analysis was performed using Revman 5.2 and STATA 10.1 software. Results: A total of 5,017 cases and 4,869 controls in 12 case-control studies were included in this meta-analysis. When all groups were pooled, there was no evidence that the P275A polymorphism had a significant association with PCa under dominant (OR=0.93, 95%CI=0.81-1.06, and p=0.28), co-dominant (homogeneous OR=0.97, 95%CI=0.56-1.68, and p=0.92; heterogeneous OR=0.93, 95%CI=0.74-1.15, and p=0.49), recessive (OR=1.10, 95%CI=0.65-1.87, and p=0.73), over-dominant (OR=0.93, 95%CI=0.75-1.15, and p=0.50), and allelic (OR=0.95, 95%CI=0.77-1.16, and p=0.61) genetic models. For stratified analyses by ethnicity and study design, no significant associations were found in the white race, the yellow race, the black race and mixed ethnicity, and the population-based case-control (PCC) and hospital-based case-control (HCC) studies under all genetic models. Conclusions: Based on our meta-analysis, the P275A polymorphism in the MSR1 gene is unlikely to be a risk factor for PCa.

Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells

  • Kim, Ji Sung;Kim, Yong Guk;Pyo, Minji;Lee, Hong Kyung;Hong, Jin Tae;Kim, Youngsoo;Han, Sang-Bae
    • 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.

The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis

  • Kim, Yunna;Cho, Seung-Hun
    • Journal of Ginseng Research
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    • v.45 no.3
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    • pp.420-432
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    • 2021
  • Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

A study on the comparison of preclinical and post-training satisfaction of dental technology students in COVID-19 (코로나19 상황에서 치기공과 학생들의 임상실습 전 기대도 및 실습 후 만족도 비교에 관한 연구)

  • Hwang, Jae-Sun
    • Journal of Technologic Dentistry
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    • v.44 no.2
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    • pp.38-46
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    • 2022
  • Purpose: This study aims to confirm the effect of clinical practice on dental technology students by comparing preclinical expectations and post-training satisfaction of dental technology students in Suwon-si, Gyeonggi-do during the coronavirus disease pandemic. Methods: This study included students enrolled in the Department of Dental Technology of D University in Suwon-si, Gyeonggi-do. The purpose of the study was explained in advance and 70 students agreed to participate in the survey. IBM SPSS Statistics version 18.0 was used for data analysis and the significance level was tested at p=0.05. Results: There were significant differences in clinical practice content, operation, institutional expectations, and satisfaction. Conclusion: Based on the differences in expectations and satisfaction in this study, schools, industries, and associations can study ways to increase satisfaction in terms of clinical practice content, operation, and institution to present directions for dental technology and clinical practice.