• Journal of Life Science
• /
• v.26 no.10
• /
• pp.1207-1213
• /
• 2016

Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.776-784
• /
• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Journal of Life Science
• /
• v.28 no.11
• /
• pp.1361-1368
• /
• 2018

Inflammation is the most common condition in the human body. Tissue damage triggers inflammation, together with vasodilation and increased blood flow at the inflamed site, resulting in edema. Inflammatory responses are also triggered by lipopolysaccharide (LPS), a Toll-like receptor Enterococcus faecalis, a gram-positive organism, has been reported to possess immunomodulatory and preventive activities; however, its use may present risks of sepsis and other systemic infections. Heat-killed Enterococcus faecalis (EF-2001) has been reported to induce antitumor activity, but its effects on inflammation are not known. In the present study, we investigated the effect of EF-2001 on LPS-induced macrophage inflammatory responses. EF-2001 treatment reduced nitric oxide (NO) production, indicating suppression of inflammatory reactions. EF-2001 showed no cytotoxicity in macrophages. Further investigation of the anti-inflammatory mechanism of EF-2001 indicated that EF-2001 reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. EF-2001 also reduced f the LPS induction of several inflammatory molecules involved in the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) and mitogen-activated protein kinase pathways, including ERK, JNK, and p38 phosphorylation, in a concentration-dependent manner. Additionally, EF-2001 inhibited Akt phosphorylation and increased the expression of the inhibitory ${\kappa}B$ ($I{\kappa}B$) protein, an inhibitor of $NF-{\kappa}B$. EF-2001 also inhibited the nuclear translocation of p65. These results suggest that EF-2001 has anti-inflammatory properties and may be useful for treating inflammatory diseases.

• Journal of Life Science
• /
• v.29 no.1
• /
• pp.112-117
• /
• 2019

Herbal medicines are widely used as therapeutic products in many countries. Corni fructus (CF), the dried ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae), has been used for thousands of years in traditional medicine and has been reported to be effective for the prevention and treatment of various diseases, such as kidney diseases and diabetes. Recent research on CF has documented a wide spectrum of therapeutic properties, which include anti-inflammatory, ant-oxidative, immunomodulatory, and anti-cancer effects. However, there is no information on its safety. Therefore, in this study, the toxicity of water extract of CF to ICR mice was investigated. The mice received a single dose of water extract of CF (1,000, 2,000, and 5,000 mg/kg of body weight) via the oral route. Mortality, clinical signs, body weight changes, gross findings, and weights of the principal organs after 14 d were then assessed. The results revealed no adverse effects of CF as determined by clinical signs, body weights, or organ weights and no gross pathological findings in any of the treatment groups. These results suggest that the 50% lethal dose and approximated lethal dose of CF extract is over 5,000 mg/kg. The findings provide scientific evidence for the safety of CFs.

• Radiation Oncology Journal
• /
• v.21 no.1
• /
• pp.54-65
• /
• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.5
• /
• pp.1012-1021
• /
• 1998

Background : It is known that airway inflammation is present in most patients with asthma, but the relationship between symptoms and the severity and nature of airway inflammation has not been established. Cough variant asthma is defined as an asthma in which the dominant symptom is cough, and the condition can be successfully treated with inhaled steroids. This study was performed to evaluate the time course of bronchial responsiveness according to an inhaled anti-inflammatory therapy and the factors which affect the resolution of bronchial responsiveness, and an efficacy of nedocromil to cough asthma. Method: A prospective study for the investigation of bronchial responsiveness according to an inhaled anti-inflammatory treatment in sixty-one cough asthmatics was performed. Twenty-three entered budesonide ($400{\mu}g{\times}2/day$), twenty-two entered nedocromil ($4mg{\times}2/day$) and sixteen patients entered combined group. The bronchial hyperresponsiveness (BHR) was estimated by methacholine challenge test using counted breath method. The symptom was estimated by 'symptom score'. Reevaluation of BHR and symptom was performed at 2 month after treatment, and if BHR was not resoluted at this time, regarded as a non-responder, and then follow-up of BHR and symptom was performed at 4- and/or 6 month after treatment. Results: The improvement of BHR and symptom was significant in 2 month (p<0.05), but there was no change of them during follow-up period of 4- and/or 6 month in non-responders. In comparison of allergic markers such as serum total IgE, peripheral eosinophil count and skin test reactivity between responders and non-responders, there was no difference in each other. However, in comparison of other factors such as cumulative pack-years, symptom duration, age, gender, and the initial degree of PC20, there was a significant difference in each other(p<0.05). The percent of patients with the resolution of BHR in 2 month was not different in each group(p=0.95). There was no significant difference in the degree of improvement of BHR and symptom in each group. Conclusion: Bronchial responsiveness and symptom was not significantly improved in non-responders during follow-up period of 4- and/or 6 month. The effect of inhaled nedocromil was equivalent to that of inhaled steroid in cough asthmatics, and the response to combined treatment is not superior to that achieved by either of these agents used alone.