• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.648-657
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• 2015

H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

• Journal of Embryo Transfer
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• v.31 no.3
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• pp.169-177
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• 2016

There is a growing interest in the application of primary hepatocytes for treatment of liver diseases in humans and for drug development. Several studies have focused on long-term survival and di-differentiation blocking of primary hepatocytes in an in vitro culture system. Therefore, the present study also aimed to optimize an in vitro culture system using primary rat hepatocytes. Primary rat hepatocytes from 6-week-old male Crl:CD rats were isolated using a modified two-step collagenase perfusion. Healthy $3.5{\times}10^6$ primary rat hepatocytes were seeded into a 2 dimensional (2D) culture in a 25T culture flask coated with collagen type I or into a 3D culture in a 125-ml spinner flask for 7 days. Production of plasma protein (ALB and TF), apoptosis (BAX and BCL2), and CYP (CYP3A1) related genes were compared between the 2D and 3D culture systems. The 3D culture system had an advantage over the 2D system because of the relatively high expression of ALB and low expression of BAX in the 3D system. However, the level of CYP3A1 did not improve in the 3D culture with and without the presence of a dexamethasone inducer. Therefore, 3D culture has an advantage for albumin production and primary rat hepatocyte survivability, but a low expression of CYP3A1 indicated that primary rat hepatocytes require a high-density culture for stress reduction by continuous flow.

• Journal of Life Science
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• v.27 no.1
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• pp.95-99
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• 2017

A previous study demonstrated that four kinds of natural compounds, Corydaline, (${\pm}$)-Car-3-ene-2,5-dione, cinobufagin, and corilagin, enhanced the gene expression of ERAP1 and FOXO1 (DFA16) more than two-fold in a cell culture system. In this study, the experimental food was made finally 30 ml in which included 1% agar, 5% sucrose, and each natural compound $20{\mu}l$. A fruit fly of Drosophila melanogaster fed a natural product for 4 hr after 4 hr starvation. Both natural compounds of Cinobufagin and Corilagin induced 6-8 days more survival comparing than it controls group. The resulting fruit flies were estimated the gene expression of ERAP1 and FOXO1 by RT-PCR that also demonstrated meaningful results with the same lifespan results. Cinobufagin from BufonisVenennumis has $C_{26}H_{34}O_6$ molecular formula and 442 kDa molecular weight. Corilagin from Euphorbiapekinensisis has $C_{27}H_{22}O_{18}$ molecular formula and 634 kDa molecular weight. The two types of natural products screened in this study will be used in the early diagnosis and treatment of insect industry in the near future. In addition, the natural products will be used in longevity experiments in a mouse model. The results may give one of the clues for studying new drug development candidates of the longevity.

• Radiation Oncology Journal
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• v.36 no.1
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• pp.17-24
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• 2018

Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

• Health Policy and Management
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• v.5 no.2
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• pp.35-69
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• 1995

The managerial environment of hospitals in Korea characterized by low levels of medical insurance fees is worsening by increasing government regulations as to the utilization of medical services, rising costs of labor, material, and medical equipments, growing patient expectations concerning the quality of services, and escalating competitions among large hospitals in the market. Hospitals should seek for their survival strategies in this harsh environment and they should have information about costs of their products in doing so. However, it has not been available due to the complexity of the production process of hospital services. The objectives of this study were to develop a service-based cost accounting model and to apply the developed model to a study hospital to obtain cost information of hospital services. A model commonly used for the job-order product cost accounting in the manufacturing industry was modified for the use in hospitals in Korea. Actual costs, instead of standard costs, incurred to produce a unit of services during a given period of time were estimated in the model. Data required to implement the model included financial information, statistics for the allocation of supportive cost center costs to final cost centers, statistics for the allocation of final cost center costs to services, and the volume of each services charged to patients during a study period. The model was executed using data of a university teaching hospital located in Seoul for the fiscal year 1992. Data for financial information, allocation statistics fo supportive service costs, and the volume of services, most of them in electronic form, were available to the study. Data for allocation statistics of final cost center costs were collected in the study. There were 15 types of evaluation and management service, 2, 923 types of technical service, and 2, 608 types of drug and material service charged to patients in the study hospital during the fiscal year 1992. Labor costs of each of seven types of pesonnel, material costs of 611 types of drugs and materials, and depreciation costs of 212 types of medical equipments, miscellaneous costs, and indirect costs incurred in producing a unit of each services were estimated. Medical insurance fees for basic services such as evaluation and management of inpatients and outpatients, injection, and filling prescriptions, and for operating procedures were found to be set lower than costs. Infrequent services which use expensive medical equipments showed negative revenuse as well. On the other hand, fees for services not covered by the insurance such as CT, MRI and Sonogram, and for laboratory tests were higher than costs. This study has a significance in making it possible for a hospital to obtain cost information for all types of services which produced income based on all types of expenses incurred during a given period of time. This information can assist the management of a hospital in finding an effective cost reduction strategy, an efficient service-mix strategy under a given fee structure, and an optimum strategy for within-hospital resource allocations.

• Journal of Life Science
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• v.28 no.1
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• pp.116-129
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• 2018

Living creatures possess long-conserved mechanisms to maintain homeostasis in response to various stresses. However, chronic and continuous exposure to stress can result in the excessive production of stress hormones, including catecholamines, which have harmful effects on health. Studies on the relationship between the sympathetic nervous system (SNS) and cancer have been conducted based on the traditional hypothesis that stress can promote cancer progression. Many preclinical and epidemiological studies have suggested that the regulation of ${\beta}$-adrenergic signaling, which mediates SNS activity, can suppress the progression of solid tumors. SNS activation has highly pleiotropic effects on tumor biology, as it stimulates oncogenes, survival pathways, the epithelial - mesenchymal transition, and invasion. Moreover, it inhibits DNA repair and programmed cell death and regulates the tumor microenvironment, including immune cells, endothelial cells, the extracellular matrix, mesenchymal cells, and adipocytes. Although targeted therapies on the molecular basis of tumor proliferation are currently receiving increased attention, they have clinical limitations, such as the compensatory activation of other signaling pathways, emergence of drug resistance, and various side effects, which raise the need for pleiotropic cancer regulation. This review summarizes the effects of the SNS on the development and progression of cancer and discusses the clinical perspectives of ${\beta}$-blockade as a novel therapeutic strategy for this disease.

• Journal of Life Science
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• v.12 no.5
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• pp.610-621
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• 2002

Conserved genes are importantly used to understand the major function in survival and replication of living organism. This study was focused on identification of conserved genes in microbial species and measuring the degree of conservation. For this purpose, in silico analysis was performed to search conserved genes based on the conservation level within microbial species. The ortholog list of COGs (Clusters of Orthologous Groups of proteins) in NCBI was used and whole genomes of 43 microbial species were included in that list. The distance value, derived from CLUSTALW multiple alignment program, was used as a descriptor of the conservation level of orthologs. It was revealed that 43 microbial genomes hold 72 conserved orthologs in common. The majority(72.2%) of the conserved genes was related to "translation, ribosomal structure and biogenesis" functional category. A GTPase-translation elogation factor(COG0050) was the best conserved gene from the distance value analysis. The 72 conserved genes, found in this research, would be useful not only to study minimal function genes but also new drug target among pathogens and to make a model of the virtual cell.tual cell.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1693-1697
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• 2012

Objective: To explore the effect on radiosensitivity of arsenic trioxide ($As_20_3$) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of $As_20_3$ was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of $IC_{50}$ value and choice of 20% of the $IC_{50}$ as the experimental drug concentration. Blank control, $As_20_3$, hyperthermia, radiotherapy group, $As_20_3$ + hyperthermia, $As_20_3$ + radiotherapy, hyperthermia + radiotherapy and $As_20_3$ + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: $As_20_3$ exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an $IC_{50}$ of 18.7 ${\mu}mol/L$. After joint therapy of $As_20_3$ + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the $G_2$/M phase, and as the ratio of cells in $G_0/G_1$ and S phases decreased, cell death became more pronounced. Conclusion: $As_20_3$ and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, $As_20_3$ and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.909-914
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• 2012

Background: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. Methods: We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250mg/day, gefitinib group) or with concomitant WBRT (40Gy/20f/4w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. Results: The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease control rate of BM was 71.1% in gefitinib-WBRT group and 42.2% in gefitinib group (P=0.006). The median time to progression of BM was 10.6 months in gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median overall survival(OS) of gefitinib-WBRT and gefitinib alone group was 23.40 months and 14.83 months, respectively (HR, 0.432, P=0.002). Conclusion: Gefitinib plus concomitant WBRT had higher response rate of BM and significant improvement in OS compared with gefitinib alone in treatment of BM from NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3431-3436
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• 2016

Background: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator. Materials and Methods: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 18-70 years. Quantitative Real Time Polymerase Chain Reaction (q-RT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters. Results: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P < .05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04). Conclusions: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.