• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.687-692
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• 2012

Schizandra chinensis extract has been known to possess a variety of efficacy including antitumor. However, it remains unclear how schizandrin, which is a major biological active ingredient of Schizandra chinensis, exerts antitumor effect. This study was designed to investigate the mechanism by which schizandrin inhibits tumor growth and metastasis. In in vivo test using tumor model mice injected with B16BL6 cell line, mice treated with 10 and 100 ${\mu}g/ml$ schizandrin showed a significant inhibition by $73.79{\pm}6.43%$ and $90.46{\pm}1.72%$, respectively, compared with positive tumor controls. Schizandrin did not exert a significant toxicity for the normal cells (HUVECs) and tumor cell lines (A549, B16BL6, Du145, Huh7). Treatment with schizandrin at 10 and 100 ${\mu}g$/head significantly inhibited the tumor-induced angiogenesis by $68.04{\pm}32.21%$ and $103.8{\pm}34.99%$ compared with the positive control group, respectively. Using in vivo lung metastasis model, tumor metastasis assay revealed that 10 and 100 ${\mu}g$/head schizandrin significantly decreased the metastatic lung tumor by $37.51{\pm}8.15%$ and $75.53{\pm}4.38%$ compared with positive controls, respectively. On the other hand, schizandrin did not affect the adherence of B16BL6 cell line to extracellular matrix protein. These results demonstrate that schizandrin exerts inhibitory effect on tumor growth and metastasis by inhibiting angiogenesis. This study thus suggest that schizandrin may be a candidate molecule target for cancer drug development.

• Journal of Life Science
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• v.25 no.12
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• pp.1377-1383
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• 2015

Scopoletin is a component of several plant such as Erycibe obtusifolia, Aster tataricus, Foeniculum vulgare and Brunfelsia grandiflora. It was reported to have anti-angiogenesis and anti-allergy effects. In this study, the anti-inflammatory effect of scopoletin was investigated in Raw264.7 cells, mouse macrophages. The effects of scopoletin on phagocytosis and nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced inflammatory responses. It was observed that scopoletin exerted inhibitory effects on both phagocytosis and NO production. In addition, scopoletin decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) which were related to NO and prostaglandin E2 (PGE2) production. In particular, the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression levels of IL-1β, IL-6 were remarkably decreased by treatment with scopoletin. Furthermore, the content of TNFα produced by macrophage was decreased in the presence of scopoletin at 8 hr. These results indicate that the anti-inflammatory effect of scopoletin could exert by inhibiting the expression of pro-inflammatory cytokines in Raw264.7 cells stimulated with LPS. The above results suggest scopoletin could be a new remedial agent for anti-inflammation through inhibition of iNOS, COX-2, IL-1β, IL-6 and TNF-α expressions as well as supression of phagocytosis and NO production.

• Journal of Chest Surgery
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• v.36 no.10
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• pp.711-720
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• 2003

Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

• Journal of Chest Surgery
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• v.32 no.4
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• pp.333-340
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• 1999

Background: Plasminogen activator inhibitor-1(PAI-1) is known as the primary physiological inhibitor of tissue-type plasminogen activator(t-PA) in the plasma, and is present within the atherosclerotic vessels. Increased plasma levels of PAI-1 are one of the major disturbances of the hemostatic system in patients with diabetes and/or hypertension, and may have multiple interrelations with the important risk factors in the development of atherosclerosis. This study was performed to determine whether altered gene expression of PAI-1 occurs within the arterial wall, and thereby potentially contributing to the increase of cardiovascular risks associated with diabetes and/or hypertension. Material and Method: The aortic vascular smooth muscle cells of the rat were exposed to 22 mM glucose, angiotensin II, and insulin increased PAI-1 mRNA expression with the use of Northern blotting were examined. Also examined were the effects of 22 mM glucose, angiotensin II and insulin on the growth of the rat's aortic smooth muscle cells by using MTT assay. Result: Twenty-two mM glucose treatment increased the PAI-1 mRNA expression in a time- and dose-dependent manner. Aniotensin II treatment synergistically increased the glucose-induced PAI-1 mRNA expression. In contrast, addition of insulin attenuated the increase of 22 mM glucose and angiotensin II induced PAI-1 mRNA expression. Furthermore, treatment of 22 mM glucose, angiotensin II and insulin resulted in a significant increase in cell numbers. This study demonstrated that 22 mM glucose and angiotensin II have a synergistic effect in stimulating the PAI-1 mRNA expression and in the cell growth of the rat's aortic smooth muscle cells. Conclusion: Elevation of glucose and angiotensin II may be important risk factors in impairing fibrinolysis and developing atherosclerosis in diabetic patients.

• Food Science and Industry
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• v.53 no.1
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• pp.2-32
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• 2020

In recent years, significant importance has been given to chitooligosaccharides (COS) due to its potent notable biological applications. COS can be derived from chitosan which is commonly produced by partially hydrolyzed products from crustacean shells. In order to produce COS, there are several approaches including chemical and enzymatic methods which are the two most common choices. In this regard, several new methods were intended to be promoted which use the enzymatic hydrolysis with a lower cost and desired properties. Hence, the dual reactor system has gained more attention than other newly developed technologies. Enzymatic hydrolysis derived COS possesses important biological activities such as anticancer, antioxidant, anti-hypersentive, anti-dementia (Altzheimer's disease), anti-diabeties, anti-allergy, anti-inflammatory, etc. Results strongly suggest that properties of COS can be potential materials for nutraceutical, pharmaceutical, and cosmeceutical product development.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.15-25
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• 1982

It was undertake to investigate the factors involved in the micro thrombus formation in the plasma from the patients with cerebrovascular disease(CVD) and the in vitro actions of sodium nitroprusside on the platelet aggregate formation. 1) The microthrombus formation in the plasma from CVD was significantly enhanced, in comparison with that from the healthy volunteers. 2) Both lipid peroxide and cathepsin D in the plasma from CVD were higher than those levels from the healthy volunteers. 3) Whereas the platelets from healthy individuals showed less aggregation activity in response to ADP in the second phase those from CVD revealed the enhanced aggregating response to ADP. 4) When the bovine basilar artery, rabbit aorta and human umbilical artery were pretreated with $K^+-free$ PSS, ouabain, 13-hydroperoxylinoleic acid(13-HPLA) and cadmium they markedly enhanced the platelet aggregability respectively. 5) Platelet aggregation induced by $K^+-free$ PSS-treated bovine basilar artery was decreased by sodium nitroprusside in a dose-dependent manner, but not by either hydralazine. 6) Both dibutyryl cyclic AMP and 8-bromo cyclic GMP had the inhibitory action on the platelet aggregation. However, the latter had more prominent action than former. The antiaggregating effect by sodium nitroprusside was antagonized by pretreatment with methylene blue, but not by hemoglobin. These results provide the evidences for the therapeutic use of sodium nitroprusside in the emergency of cerebrovascular disease and in remains the further study of the clinical therapy with it.

• Clinical and Experimental Pediatrics
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• v.46 no.6
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• pp.548-553
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• 2003

Purpose : Matrix metalloproteinase(MMP)-9 is known to breakdown the blood-brain barrier by degrading the extracellular matrix of the subendothelial basement membrane in meningitis. Tissue inhibitor of metalloproteinase(TIMP)-1, a known inhibitor of MMP-9, has been postulated to inhibit the proteolytic activity of MMP-9 by bindng to MMP-9, but their interaction has not been fully understood yet. So far, there have been some reports on the relationship of MMP-9 and TIMP-1 in bacterial meningitis, but few reports in viral meningitis. Furthermore, there has been no report on this in Korea. We investigated the concentrations of MMP-9 and TIMP-1 in cerebrospinal fluid (CSF) and serum of patients with viral meningitis and control subjects, and evaluated their relationship with other clinical parameters of meningitis. Methods : CSF and blood were obtained from 25 subjects with viral meningitis and 14 control subjects. After centrifugation, supernatants were stored at $-20^{\circ}C$ and we assayed concentrations of MMP-9 and TIMP-1 by the sandwich ELISA method. Results : Concentrations of CSF MMP-9 and TIMP-1 were significantly elevated in patients with viral meningitis, when compared with those in control subjects. Their serum levels showed no differences between the two groups. MMP-9 levels were closely correlated with TIMP-1 levels in the CSF($r_s=0.42$, P<0.05). CSF MMP-9/TIMP-1 ratios were significantly higher in patients with viral meningitis than those in the control subjects(P<0.05). Both CSF MMP-9 and TIMP-1 levels positively correlated with CSF total leukocyte counts($r_s=0.43$, P<0.05, $r_s=0.48$, P<0.05). TIMP-1 levels positively correlated with total protein concentrations in the CSF($r_s=0.43$, P<0.05). Conclusion : MMP-9 and TIMP-1 may play an important role in the breakdown and maintenance of BBB in viral meningitis, respectively.

• Journal of Chest Surgery
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• v.36 no.1
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• pp.7-14
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• 2003

Cyclin I plays a pivotal role in the regulation of G1-S transition and could consequently be a deregulated molecule in tumors. The activity of the cdk2-cyclin E complex is increased by degradation of cdk inhibitor p27kip1. Little is known about the expression and prognostic significance of cyclin E and p27 in non-small cell lung cancer(NSCLC). Material and Method: The expression of cyclin E and p27 in eighty-one cases of resected stage I NSCLC tissues and its relation to major clinico-pathological factors, including histology, differentiation, size of tumor, pleural invasion and survival rate were studied and analyzed. Immunohistochemical analysis with monoclonal antibodies specific for cyclin E and p27 were performed by ABC method. Result: Expression rates of cyclin E and p27 in stage I NSCLC tissues were 29.6% and 28.4% respectively. Cyclin E was expressed higher in cases of pleural invasion(p=0.04), and p27 was expressed higher in diameter of tumor less than 3cm(p=0.015). The 5-years survival rate was lower in cases of Positive expression of cyclin E than in cases of negative expression of cyclin E(44.4% vs 68.2%, p=0.015), and the 5-years survival rate was 72.2% in positive expression of p27 and 56.2% in negative expression of p27(p=0.09). The 5-years survival rate was higher in negative expression of cyclin E and positive expression of p27 than in cases of positive expression of cyclin I and negative expression of p27 (73.5% vs 36.3%, p=0.0029). In multivariate analysis, expression of cyclin I was an unfavorable prognostic factor(RR=3.578, p=0.006) and p27 was a favorable prognostic factor(RR=0.183, p=0.019) independently. Conclusion: Cyclin E and p27 may play a pivotal role for the biological behavior of stage I NSCLC, so that the expressions of cyclin I and p27 nay be new prognostic markers.

• Journal of Life Science
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• v.29 no.8
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• pp.904-915
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• 2019

Prostate cancer (PCa) is one of the most metastatic tumor. Although hormone therapy or surgical castration is mostly conducted to treat PCa, it has a lot of side effects. Recently, many researchers have been exploring the tumor microenvironment to remedy these circumstances. Immune cells, especially macrophages, are an important composition of the tumor microenvironment. Under normal conditions, macrophages exhibit mild tumoricidal activity against tumors. However, once activated by interferon gamma or lipopolysaccharides, macrophages can kill cancer cells directly or indirectly by secreting cytokines and chemokines. In this study, murine macrophage RAW 264.7 cells were treated with Phellinus linteus extract. To analyze their pro-inflammatory phenotype, we were used several assays such as a real-time polymerase chain reaction, an enzyme-linked immunosorbent and nitric oxide assay. Prostate cancer cells were treated with the RAW 264.7-conditioned media, which was identified as a pro-inflammatory nature, for 48 h, and the expression of epithelial-mesenchymal transition (EMT)-related genes was determined. Not only N-cadherin, Snail, Twist, Slug, and Cadherin 11, which are mechenchymal-related proteins, were decrease, but epithelial marker of E-cadherin was increased. In addition, the mRNA level of vimentin, ccl2, and vegfa were decreased, as the EMT is closely related to the migration and invasion of cancer cells. In conclusion, the RAW 264.7-conditioned media stimulated with P. linteus extract inhibited migration and invasion and regulated the EMT pathway in human prostate cancer cells.