• Korean Journal of Food Science and Technology
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• v.38 no.5
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• pp.707-711
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• 2006

Phase 2 enzymes are transcriptionally induced by a wide variety of chemical agents and natural products, and their induction plays a critical role in protection against chemical carcinogens and other toxic xenobiotics. The activity of the methanol extract and fractions of paprika (Capsicum annuum L.) was examined in murine Hepa1c1c7 cells for the induction of nicotinamide adenine dinucleotide (phosphate) NAD(P)H/quinone reductase (QR). The ethyl acetate (EtOAc) fraction induced QR activity in a dose-dependent manner in the concentration range of 10 to $500\;{\mu}g/mL$ with a maximum of a 3.3-fold increase in induction. The EtOAc fraction also showed high QR induction potency in Ah-receptor-defective mutant of Hepa 1c1c7 cells ($BP^rcl$ cells), which indicates that this fraction is a monofunctional inducer of QR. These results suggest that useful cancer chemopreventive materials could be isolated from EtOAc fraction of Paprika.

• Journal of Hospice and Palliative Care
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• v.20 no.2
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• pp.81-92
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• 2017

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation that is usually progressive. It is a major cause of morbidity and mortality worldwide, leading to substantial and increasing economic and social burden. Palliative care for COPD patients aims to reduce symptoms and exacerbations and improve exercise tolerance and quality of life. It is difficult to make a prognosis for COPD patients due to the variable illness trajectory and advanced care of patients. However, severity of breathlessness, assessment of lung function impairment, and frequency of exacerbations can help to identify palliative care needs and determine effective methods to mitigate symptoms, which is discussed in this paper. In these patients, it is recommended to provide individualized palliative care along with curative/restorative care at the onset of COPD symptoms. Before launching a palliative care system in Korea, it is necessary to prepare pulmonary rehabilitation resources, patient-centered communication, timely palliative responsiveness, and a program for effective advanced care planning. A multidisciplinary approach involving collaboration with not only the respiratory and palliative care teams but also primary care offers a new model of care for these patients and should be considered with a priority.

• Radiation Oncology Journal
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• v.6 no.1
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• pp.93-99
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• 1988

Some modern accerelators provide a dual energy for photon beam treatment. The main advantages of dual energy in the treatment of rectosigmoid or rectal cancer are as fellows. 1. Dose in the critical organ such as small intestine, bladder and genital organ are reduced. 2. Presacral and perineal area is fully covered. Dose distribution analysis such as calculation of dose in a target volume, isocenter, $D_{nax}$ and dose spectrum in any region of interest are possible. Examples of plan are given and results are discussed.

• Proceedings of the Microbiological Society of Korea Conference
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• 2007.05a
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• pp.120-122
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• 2007

All living organisms use numerous signal-transduction pathways to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we employed Cryptococcus neoformans as a model system to understand how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental stresses, including osmoticshock, UV, high temperature, oxidative stress and toxic drugs/metabolites. The stress-activated p38/Hog1 MAPK pathway is structurally conserved in many organisms as diverse as yeast and mammals, but its regulation is uniquely specialized in a majority of clinical Cryptococcus neoformans serotype A and D strains to control differentiation and virulence factor regulation. C. neoformans Hog1 MAPK is controlled by Pbs2 MAPK kinase (MAPKK). The Pbs2-Hog1 MAPK cascade is controlled by the fungal "two-component" system that is composed of a response regulator, Ssk1, and multiple sensor kinases, including two-component.like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. We also identified and characterized the Ssk2 MAPKKK upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for differential Hog1 regulation between the serotype D sibling f1 strains B3501 and B3502 through comparative analysis of their meiotic map with the meiotic segregation of Hog1-dependent sensitivity to the fungicide fludioxonil. Ssk2 is the only polymorphic component in the Hog1 MAPK module, including two coding sequence changes between the SSK2 alleles in B3501 and B3502 strains. To further support this finding, the SSK2 allele exchange completely swapped Hog1-related phenotypes between B3501 and B3502 strains. In the serotype A strain H99, disruption of the SSK2 gene dramatically enhanced capsule biosynthesis and mating efficiency, similar to pbs2 and hog1 mutations. Furthermore, ssk2, pbs2, and hog1 mutants are all hypersensitive to a variety of stresses and completely resistant to fludioxonil. Taken together, these findings indicate that Ssk2 is the critical interface protein connecting the two-component system and the Pbs2-Hog1 pathway in C. neoformans.

• Journal of Life Science
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• v.26 no.1
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• pp.91-100
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• 2016

Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neo-vascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.168-172
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• 2003

Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

• Korean Journal of Food Science and Technology
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• v.33 no.6
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• pp.656-663
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• 2001

The most representative nitrosamine derived from nicotine, nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), has been reported to cause lung cancer in A/J mice. It has been also demonstrated that NNK-induced lung tumorigenesis involves $O^6-methylguanine(O^6MeG)$ formation, leading to $GC\;{\rightarrow}\;AT$ transitional mispairing during DNA replication. Our in vitro experiment, modified from the method of DBA assay, examined the ability of phyto-extract mixture to inhibit the metabolism of nicotine to nitrosamines. The production of nitromorpholine from morpholine was inhibited about 75% at the concentration of 20 mg/mL of phyto-extract mixture, which was lower than vitamine C and green tea powder. NNK, which is a pro-carcinogen in laboratory animals, is hydroxylated primarily in liver and lung by CYP 1A2, 2A6 and 3A4. A critical phase. of NNK activation is its change to an unstable metabolite methyl-diazohydroxide via CYP-mediated ${\alpha}-hydroxylation$; and then it provides a methyl group to the DNA to form DNA adducts which can easily induce mutations. $Aroclor^R$ 1254 was used to induce CYPs in the liver of a Sprague-Dawley rat. The ability of various test samples to inhibit CYPs that participate in NNK activation was evaluated, following the removal of the liver from the rat. Microsomal CYPlA2 catalyzing the conversion of NNK into strong carcinogenic chemicals was inhibited more efficiently by phyto-extract mixture than green tea powder. These results indicate that phyto-extract mixture can be used to reduce $O^6MeG$ DNA adducts for chemoprevention.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.86-92
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• 2014

Cordycepin is the major functional component of Cordyceps species and is widely used in traditional oriental medicine. Cordycepin has been shown to possess many pharmacological properties, such as enhancement of immune function along with anti-inflammatory, antioxidant, anti-aging, and anti-cancer effects. Here, we investigated the inhibitory effects of cordycepin on cell migration and invasion, which are two critical cellular processes that are often deregulated during metastasis, using HCT116 human colorectal carcinoma cells. According to our data, cordycepin at non-cytotoxic concentrations markedly inhibited the motility and invasiveness of HCT116 cells in a time-dependent manner. RT-PCR and Western blotting results indicated that cordycepin reduced the levels of claudin proteins, which are major components of tight junctions (TJs), and induced tightening of TJs. Cordycepin also attenuated the expression and activities of matrix metalloproteinases (MMPs)-2 and -9, whereas levels of tissue inhibitor of metalloproteinases (TIMPs)-1 and -2 were simultaneously elevated. These findings suggest that cordycepin reduces the migration and invasion of HCT116 cells by modulating the activities of TJs and MMPs.

• BMB Reports
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• v.53 no.6
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• pp.323-328
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• 2020

Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.

• Progress in Medical Physics
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• v.13 no.1
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• pp.32-36
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• 2002

For Intensity Modulated Radiation Therapy(IMRT), the spatial resolution of intensity map(IM) is limited by the width of multi-leaf collimator, which would make an effect on the conformity of the target, as well as organs at risk. Several Methods are suggested to increase the spatial resolution, which can be categorized by the hardware-dependent technique and the software-based technique. However the best solution might be to make the width of MLC finer. it has several obstacles in the respects of technical difficulty and cost. This preliminary study is designed to investigate the clinical effectiveness of the virtual-micro IMRT(VMIMRT) technique, one of the software-based technique. A particular intensity map was created, which has 42$\times$54 pixel dimension ,0.5cm pixel size and 15 intensity levels. Using this intensity map, segment fields of IMRT were generated with 1$\times$lcm, 0.5$\times$1cm, 0.5$\times$0.5cm(VMIM) beamlet size, respectively As results, we found that there was no evidence of improvement for VMIMRT, compared with the 0.5$\times$lcm beamlet size which can be delivered by 1cm width MLC. The reason seems to be due to the constraint of VMIMRT. Further study is required to prove the benefit of the VIMRT in clinical case like head and neck cancer, where is expected that higher resolution than 1cm is necessary.