• The Journal of Korean Medicine
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• v.19 no.2
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• pp.337-372
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• 1998

To evaluate the effects of Injinchunggantang-derivative on cell viability, cell cycle progression, and apoptosis, MTT assay, cell cycle analysis, Cpp32 protease assay, DNA fragnemtation assay, quantitative RT-PCR, and Western blotting were performed. The results were as followes. In MTT assay, etoposide+Injinchunggantang-derivative-treated cells as well as Injinchunggantang-derivative-treated cells showed higher viability than etoposide-treated cells with no time-concentration-dependence, which implied that Injinchunggantang-derivative has hepato-protective effect Cell cycle analysis showed that Injinchunggantang-derivative has no significant effect on the cell cycle. Cpp32 protease assav and DNA fragmentation assay Injinchunggantang-derivative carry inhibitory effects on apoptosis induction. It was suggested that Injinchunggantang-delivative might regulate the cell cycle, in particular $G_1$ checkpoint by blocking p53 and Watl pathway. Injinchunggantang-derivative inhibited the mRNA expressions of Cpp32, Fas, and Bcl-2, which could result in inhibition of apoptosis. These results imply that Injinchunggantang-derivative increases hepatocyte viability, and protects hepatocyte from damage by regulating the expression of genes associated with cell cycle and apoptosis, which explains the mechanism of the clinical effect of Injinchunggantang-derivative on liver diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.208-214
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• 2014

Background: In previous work, we reported that Korean Red Ginseng saponin fraction (RGSF) showed anti-inflammatory activities in vitro and in vivo. Methods: The present study investigated the radioprotective properties of RGSF by examining its effects on ionizing radiation (IR)-enhanced and lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophage cells. Results: RGSF induced strong downregulation of IR-enhanced and LPS-induced proinflammatory responses such as nitric oxide (NO) production (Inhibitory Concentration $50(IC_{50})=5.1{\pm}0.8{\mu}M$) and interleukin-$1{\beta}$ levels. RGSF was found to exert its radioprotective effects by inhibition of a signaling cascade that activated checkpoint kinase 2enuclear factor-${\kappa}B$. In addition, RGSF strongly inhibited IR-enhanced LPS-induced expression of hemoxyganase-1, implying that the latter may be a potential target of RGSF. Conclusion: Taken together, our data suggest that RGSF can be considered and developed for use as an effective radioprotective agent with minimal adverse effects.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.88-94
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• 2018

Background: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. Methods: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. Results: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). Conclusion: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

• The KIPS Transactions:PartA
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• v.10A no.2
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• pp.123-130
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• 2003

This paper presents a new striped checkpointing scheme for serverless cluster computers, where the local disks are attached to the cluster nodes collectively form a distributed RAID with a single I/O space. Striping enables parallel I/O on the distributed disks and staggering avoids network bottleneck in the distributed RAID. We demonstrate how to reduce the checkpointing overhead and increase the availability by striping and staggering dynamically for communication intensive applications. Linpack HPC Benchamark and MPI programs are applied to these checkpointing schemes for performance evaluation on the 16-nodes cluster system. Benchmark results prove the benefits of the striped checkpointing scheme compare to the existing schemes, and these results are useful to design the efficient checkpointing scheme for fast rollback recovery from any single node failure in a cluster system.

• Molecules and Cells
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• v.41 no.2
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• pp.127-133
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• 2018

Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.

• Korean Journal of Environmental Biology
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• v.23 no.1
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• pp.21-26
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• 2005

Cell response to genotoxic agents is complex and involves the participation of different classes of genes including cell cycle control, DNA repair and apoptosis. In this report, we presented a approach to characterize the cellular functions associated with the altered transcript profiles of MCF-7 exposed to low-dose in vitro gamma-irradiation. We used the method of human 2.4 k cDNA microarrays containing apoptosis, cell cycle, chromatin, repair, stress and chromosome genes to analyze the differential gene expression characterization that were displayed by radiation-exposed cell, human breast carcinoma MCF-7 cell line, such as 4 Gy 4 hr, 8 Gy 4 hr, and 8 Gy 12 hr. Among these genes, 66 were up-regulated and 49 were down-regulated. Specific genes were concomitantly induced in the results. Cyclin dependent kinase 4 (Cdk4) is induced for starting the cell cycle. This regulation is required for a DNA damage­induced G1 arrest. In addition to, an apoptotic pathways gene Bcl-w was concomitantly induced. Mismatch repair protein homologue-l (hMLH1), a necessary component of DNA mismatch protein repair (MMR), in G2-M cell cycle checkpoint arrest. The present study provides new information on the molecular mechanism underlying the cell response to genotoxic stress, with relevance to basic and clinical research.

• Journal of KIISE:Computer Systems and Theory
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• v.29 no.2
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• pp.75-86
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• 2002

The selection of the optimal checkpointing interval has been a very critical issue to implement a checkpointing recovery scheme for the fault tolerant distributed system. This paper presents a new scheme that allows a process to select the proper checkpointing interval dynamically. A process in the system evaluates the cost of checkpointing and possible rollback for each checkpointing interval and selects the proper time interval for the next checkpointing Unlike the other scheme, the overhead incurred by both of the checkpointing and rollback activities are considered for the cost evaluation and current communication pattern is reflected in the selection of the checkpointing interval. Moreover, the proposed scheme requires no extra message communication for the checkpointing interval selection and can easily be incorporated into the existing checkpointing coordination schemes.

• Korean Journal of Head & Neck Oncology
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• v.35 no.1
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• pp.13-20
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• 2019

Background/Objectives: Despite multiple approaches of treatments for salivary duct carcinoma, there has been a need for more successful treatment methods because of its poor prognosis. Treatment options like immunotherapy using new technologies have been attempted. Based on recent study results indicating that targeting programmed death receptors are effective in treating various cancers, this study aimed to identify the frequency of PD-L1 expression and its impact on survival rate in salivary duct carcinoma. Materials & Methods: We studied 33 patients with salivary gland cancer who were available for histologic specimens. We examined the expression of PD-L1 in the tissues and analyzed the association with the survival rate and the association with various clinical parameters. Results: According to this study and review of similar studies, we discovered that the expression of PD-L1 in salivary duct carcinoma was lower than other types of cancers. The impact of PD-L1 on survival rate also showed inconsistency in salivary duct carcinoma. Conclusion: Immunotherapy by PD-1/PD-L1 checkpoint blockade in salivary duct carcinoma needs further evaluation for clinical application.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.63-70
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• 2019

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.