• BMB Reports
• /
• v.47 no.4
• /
• pp.221-226
• /
• 2014

Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-$Ser^{392}$-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-$Ser^{392}$-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-$Ser^{392}$-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on $Ser^{392}$ presents an alternative for HCC chemotherapy.

• Journal of the Optical Society of Korea
• /
• v.20 no.6
• /
• pp.663-668
• /
• 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.

• Nuclear Engineering and Technology
• /
• v.53 no.4
• /
• pp.1289-1296
• /
• 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.

• Journal of Oriental Neuropsychiatry
• /
• v.32 no.2
• /
• pp.111-127
• /
• 2021

Objectives: To review and analyze clinical and preclinical evidence of effectiveness, safety, and underlying mechanisms of yokukansan (YKS), a herbal medicine, in alleviating aggression. Methods: Classical records on YKS were searched in the Korean Traditional Medicine Knowledge Database (KTMKD). By searching five electronic databases, prospective clinical studies and preclinical studies of YKS for alleviating aggression/agitation published up to March 30, 2021 were included. Results: Only two classical records on YKS were found from the KTMKD. A total of 11 clinical studies and 15 preclinical studies were found from the five electronic databases. Among 11 clinical studies, seven enrolled patients with dementia and four enrolled patients with other neuropsychiatric disorders. Most clinical studies reported significant improvement in one or more outcomes related to aggression in the YKS group after treatment. Among 15 preclinical studies, all studies except two reported a significant decrease in aggression/agitation-related behavior of YKS or yokukansankachimpihange. Suggested underlying mechanisms of YKS or yokukansankachimpihange for aggression/agitation in these studies included regulation of serotonin receptor, amelioration of abnormal glucocorticoid level related to the hypothalamic-pituitary-adrenal axis, regulation of orexin secretion, amelioration of degeneration in brain cells including glia cells, and suppression of excessive glutamatergic or dopaminergic activity. Conclusions: There were some clinical and preclinical evidence supporting the effectiveness and safety of YKS for alleviating aggression. Given that aggression is the most frequent and destructive symptoms of behavioral and psychological symptoms of dementia, applicability of YKS as a herbal medicine should be further investigated in future high-quality research.

• Korean Journal of Veterinary Research
• /
• v.63 no.4
• /
• pp.35.1-35.10
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.7
• /
• pp.3035-3042
• /
• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.7
• /
• pp.3123-3128
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.13
• /
• pp.5407-5413
• /
• 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.

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

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