• The Journal of Korean Medicine
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• v.38 no.3
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• pp.124-142
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• 2017

Objectives: This study aimed to learn what should be considered in [Guideline of Clinical Trial with Herbal Medicinal Product for Gastric Cancer)] by analyzing the existing guidelines and clinical trials. Methods: The development committee searched guidelines for herbal medicinal product or gastric cancer developed already. Then, clinical trials for gastric cancer using herbal medicine were searched. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of analysis with the regulations and guidelines of Ministry of Food and Drug Safety to suggest the issue that we will have to consider when making the [Guideline of Clinical Trial with Herbal Medicinal Product for Gastric Cancer]. Results: As a result, few guidelines for anti-tumor agent and clinical trial with herbal medicinal product were searched in the national institution homepage. In addition, 10 articles were searched by using the combination following search term; 'stomach neoplasm', 'herbal medicine', 'Medicine, Korean traditional', 'Medicine, Chinese Traditional', 'TCM', 'TKM', 'trial'. Most trials included gastric cancer participants with medical history of operation. The type of intervention was various such as decoction, granules, and fluid of intravenous injection. Comparators were diverse such as placebo, conventional treatment including chemotherapy and nutritional supplement. The most frequently used outcome for efficacy was quality of life. Besides, the symptom score, tumor response, and survival rate were used. Safety was investigated by recording adverse events. Conclusion: We found out some issue by reviewing the existing guidelines and comparing it with clinical trials for gastric cancer and herbal medicinal products. These results will be utilized for developing [Guideline of Clinical Trial with Herbal Medicinal Product for Gastric Cancer].

• Journal of Ginseng Research
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• v.36 no.1
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• pp.86-92
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• 2012

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.465-469
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• 1998

Acute respiratory failure with diffuse pulmonary infiltration was occurred in a patient with malignant lymphoma 1month after the $8^{th}$ CHOP chemotherapy. The ground glass and consolidation appearances on chest C-T in this immunodeficient patient could be presented in many clinical situations such as pneumonia by opportunistic infections (fungal, parasites, viral, and usual bacterial pathogens), anti-tumor drug's pulmonary toxicity and tumor invasion. And the other diseases of acute interstitial pneumonitis, alveolar proteinosis, BOOP, puhnonary edema and alveolar hemorrhage, which could present the same radiological findings, should included in differential diagnosis. This patient was diagnosed as the opportunistic pneumonia by Pneumocystis carinii and probably Cytomegalovirus through bronchoalveolar lavage and transbronchial lung biopsy

• The Korea Journal of Herbology
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• v.33 no.3
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• pp.55-61
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• 2018

Objectives : Artemisia capillaris Thunberg (AC) and Artemisia iwayomogi Kitamura (AI) have been used without distinguishment since ancient times due to similar appearance. In this study, we compared the inhibitory effects of AC and AI on the expression of inflammatory cytokines induced by lipopolysaccharide (LPS) in murine macrophages. Methods : AC and AI were extracted by reflux with distilled water (DW) and 70% ethanol (EtOH). We investigated the inhibitory effects of AC and AI on the expression of nitric oxide (NO), inducible NO synthase (iNOS) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) induced by LPS in macrophages. Results : Firstly, yield of the samples was higher in order of Artemisia iwayomogi DW Extract (AID), Artemisia iwayomogi 70% EtOH Extract (AIE), Artemisia capillaris DW Extract (ACD) and Artemisia capillaris 70% EtOH Extract (ACE). All of the samples were not toxic in macrophages. The inhibitory effect of the samples on LPS-induced NO expression was stronger in the order of AIE, ACE, AID and ACD. The inhibitory effect of the samples on LPS-induced inducible iNOS expression was stronger in the order of AIE, ACE and AID. Effect of ACD was same with that of AID. In addition, inhibitory effect of the samples on LPS induced $TNF-{\alpha}$expression wes stronger in the order of AIE, ACE, AID and ACD. Conclusion: These results showed that AI would be more effective than AC and 70% EtOH would be more effective than DW as an extraction solvent in inflammatory diseases.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.465-472
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• 2022

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl₂ is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl₂-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl₂-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl₂ but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl₂, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.249-261
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• 2024

New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.10 no.1
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• pp.38-42
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• 2014

A tracheostomy tube serves as airway management for patients whose respiration is impeded due to inflammation, tumor, or traumatic events. If the patients who have tracheostomy tube, visit dental clinic for dental treatments, we should consider the underlying general condition of patients and then make treatment plans according to their state. A 22-Year old male patient, who had tracheostomy tube on his neck, came to our department for comprehensive dental treatment. Mild mental retardation was observed and he was taking anti-convulsant drugs for the prevention of epileptic seizure. Multiple advanced dental caries, hopeless teeth, and impacted third molars were also observed by clinical and radiographic examination. Due to the risk of epileptic seizure and low cooperativity to tolerate the treatment, general anesthesia was recommended by physician, and the anti-convulsant drug was administrated during procedure. In this case, we aimed to report the multidisciplinary approach for the dental treatment of patient having a tracheostomy tube.

• Development and Reproduction
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• v.22 no.2
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• pp.133-142
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• 2018

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.721-727
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• 2007

Scorpion (SCP) has been clinically used for the treatment of endogenous wind to relieve convulsion, clearing away toxins, resolving hard masses and removing obstruction in the collaterals to relieve pain. Recent studies showed that scorpion toxins that affect the activating mechanism of sodium channels and indian black scorpion venom induced anti-proliferative and apoptogenic activity against human leukemic cell lines U937 and K562. There is lack of studies regarding the effects of SCP on the immunological activities. The present study was conducted to evaluate the effect of SCP on the regulatory effects of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. After the treatment of SCP MeOH extract dissolved in media for 1 h prior to the addition of lipopolysaccharide (LPS: 1 ${\mu}$g/ml), cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Inducible nitric oxide synthase (iNOS) was determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. As results, SCP inhibited the production of nitrite and nitrate (0.3 and 1.0 mg/ml), iNOS and p-$I_KB_{\alpha}$ protein, tumor necrosis factor-${\alpha}$ (0.3 and 1.0 mg/ml), interleukin-1${\beta}$ (0.3 and 1.0 mg/ml) and interleukin-6 (1.0mg/ml) in Raw 264.7 cells activated with LPS. These findings suggest that SCP can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.