• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.287-293
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• 1997

To make a stable o/w emulsion, the effects of egg lecithin as an emulsifier and polyvinylpyrrolidone (PVP) as an auxiliary emulsifier on the physical stability of emulsion were investigated. The oil-in-water emulsion system was manufactured by microfluidizer and evaluated the physical stability. Average particle size and size distribution of emulsion was measured by dynamic light scattering analyzer and interfacial tension was measured. From the interfacial tension tested, critical micelle concentration of the egg lecithin was 0.1 %w/v and optimal concentration for the preparation of emulsion was 1.0 %w/v. The mean particle size was about $0.2\;{\mu}m$ which was suitable for injections. The short-term accelerated stability studies were conducted by centrifugation, freeze-thaw method and shaking of the emulsion samples. The addition of PVP was caused the reduction in the particle size and improved the physical stability of emulsion. These results suggested that a mixed interfacial film comprising the egg lecithin and PVP was formed at the o/w interface and it was effective in preventing phase separation under thermic or mechanical stress. We used antineoplaston A10 (A10) as a model drug which is peptide and amino acid derivative having a action to the living organism against the development of neoplastic growth by a nonimmunological progress. It has a poor solubility in water and there may be a difficulty in formulation of A10. Emulsion formulation study about A10 was performed. Solubility of A10 in emulsion was about five times as high as that in water. From the results of solubility and partition coefficient, almost A10 molecules in o/w emulsion exist in the interface between oil and water.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.241-248
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• 2020

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922-mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BB-induced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.210-216
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• 2007

There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. The aim of our study is to analyze the relation between the increase in mast cell number and the expression CD34 and alpha-smooth muscle actin (${\alpha}$-SMA) in the stroma of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). We investigated a total of 29 CIN (1,2,3) and 21 SCC (microinvasive and invasive) specimens and compared the distribution of $CD34^+$ stromal cells, ${\alpha}-SMA^+$ cells, transforming growth factor-${\beta}1$ $(TGF-{\beta}1)^+$ cells, and the density of mast cells using immunohistochemistry with antibodies against CD34, ${\alpha}$-SMA, TGF-${\beta}1$, and c-Kit (CD117) respectively. Computerized image analysis was to evaluate the positive area (%) and density of the respective immunoreactive cells. In CIN $CD34^+$ cells were abundant in the stroma but no ${\alpha}-SMA^+$ cells were identified except the wall of blood vessels. $CD34^+$ cells were progressively decreased along the continuum from CIN 2 to microinvasive SCC and not observed in the stroma of invasive SCC. Whereas ${\alpha}-SMA^+$ cells were only observed in the stroma of microinvasive and invasive SCC. We found more intense TGF-${\beta}1$ expression in the increased mast cells in the stroma of invasive SCCs than that in the stroma of CIN. These results indicate that disappearance of $CD34^+$ stromal cells and appearance of ${\alpha}-SMA^+$ cells are associated with the stromal change of CIN to SCC and the transformation of $CD34^+$ stromal cells into ${\alpha}-SMA^+$ cells is mediated by TGF-${\beta}1$ secretions in the stromal mast cell of SCC.

• Journal of Nutrition and Health
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• v.38 no.1
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• pp.20-29
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• 2005

This study is conducted to determine the effects of dietary levels of corn and tuna oils on the formation of preneoplastic lesions in die-thylnitrosamine (DEN) induced rat hepatocarcinogenesis. Weanling male Sprague-Dawley rats were fed 2.5, 5, 15, 25% (w/w) corn or tuna oils. Hepatocellular carcinogenesis was induced by DEN (200 mg/kg body weight) and two-thirds partial hepactectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. Tuna oil group showed smaller area of placental glutathione S-transferase (GST-P) positive foci than com oil group. Com oil group of 25% (w/w) showed the widest area of GST -P positive foci, and tuna oil group showed significantly smaller area of GST-P positive foci than com oil in 25% (w/w) level but had no differences between oil levels. Thio-barbituric acid reactive substances (TBARS) content was the highest in 25% (w/w) level of tuna oil group fed long chain and highly polyunsaturated fatty acids. Also serum ${\gamma}$ -glutamyltranspeptidase (GGT) activities in 25% level of tuna oil group were significantly higher than by other levels. As oil contents increased, glucose 6-phosphatase (G6Pase) seems to decrease in com oil groups but remained the same in tuna oil groups. Glutathione reductase (GR) activities were significantly higher in tuna oil group, and the higher the level of tuna oil, the higher GR activities. But Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities didn't seem to be influenced by levels and kind of dietary fats. Therefore, as oil levels increased, com oil rich in n-6 fatty acids promoted carcinogenesis but tuna oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of n-3 fatty acids suppressed. Although lipid peroxidation products were elevated in 25% (w/w) tuna oil group, GST-P positive foci didn't increase. Therefore pre-neoplastic lesions might be reduced through mediation of a lipid peroxidation process in tuna oil. As fat contents of tuna oil increased, elevated GR activities may give a rise to produce more reduced glutathione in order to protect against free radical attack, and high G6Pase activities remained the same and they contributed to membrane stability. So tuna oil diet seems to protect hepatocarcinogenesis.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1399-1405
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• 2001

Objectives : Gliomatosis cerebri is an uncommon primary brain tumor characterized by diffuse neoplastic proliferation of glial cells, with the preservation of the underlying cytoarchitecture. The aim of this study is to evaluate clinical features, outcome of surgical treatment and adjuvant therapy of gliomatosis cerebri. Methods : Between Jan. 1990 and Dec. 2000, 12 patients were diagnosed with gliomatosis cerebri based on characteristic radiological and histological findings. The patients' age ranged from 18 to 77(mean 44) years and the male to female ratio was 7 : 5. Nine patients underwent decompressive surgery and three, biopsy only. Postoperative radiation therapy was given in all cases except three. In addition to radiation therapy, four patients received chemotherapy. The mean duration of follow-up period was 18.8 months. Results : The most common presenting symptom were seizure and motor weakness. The mean duration of symptom was 5.9 months. There was 5 bilateral lesions and tumor involved corpus callosum in 5, basal ganglia-thalamus in 4, and brain stem in 2. There was no operative mortality but four patients died during the follow-up. The mean survival period for 11 patients was 20.5 months from the time of diagnosis. In univariate analysis, the lesion involving corpus callosum, basal ganglia-thalamus and brain stem correlated significantly with the short length of survival(p<0.05). Also, postoperative radiation as a adjuvant therapy prolonged the patient's survival(p<0.05). Conclusions : In the management of gliomatosis cerebri patients, early detection by MR imaging, active management of increased intracranial pressure, decompressive surgical removal and postoperative adjuvant therapy such as radiation is thought to be a good treatment modality.

• Korean Journal of Veterinary Research
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• v.35 no.4
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• pp.793-807
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• 1995

This study was carried out to investigate the effects of diethyl maleate(DEM) on the carcinogenesis of forestomach and pyloric glandular stomach in rats caused by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). A total of 60 male 6-week-old Wistar rats were given twice intragastric injection of MMNG(200mg/kg BW), then were given diets containing 5% NaCl for 3 weeks until 4th week of the experiment. And then the animals of groups of 1 and 2 were placed on diets containing 0.2% DEM for 16 weeks until the end of 20 weeks of the experiment. On the other hand, the animals of groups of 3 and 4 were placed on basal diets for the same periods. The tissues of forestomach and liver of each group were frozen in liquid nitrogen and the activities of quinone reductase(QR) were determined by measurement of the dicoumarol-sensitive reduction of dichloro-indophenol by NADPH at 600nm. All rats were sacrificed at the end of 20 weeks of the experiment. Every animal was fasted for 24 hrs prior to sacrifice. The forestomach was fixed in 10% neutral phosphate buffered formalin for histology and the pyloric gland was fixed in sublimated formalin for immunohistochemistry of pepsinogen 1 altered pyloric gland(PAPG). The final body weight of the group given MNNG and treated with 5% NaCI and DEM was significantly decreased compared with that of the group 4(p<0.05). Food and water consumption rates were not significantly changed. The preneoplastic and neoplastic lesions of the forestomach given MNNG and treated with 5% NaCI and DEM were significantly increased compared to those of the group 4(p<0.0l). The incidence of PAPG in the groups treated with 0.2% DEM was significantly increased compared with that of the group 4(group 1:p<0.01, group 2:p<0.05). The activities of QR of forestomach in the groups treated with 0.2% DEM were significanitly increased compared with those of the group 4(p<0.001), but those of liver were not significant. These results indicate that DEM exert the enhancing effect of forestomach and glandular stomach carcinogenesis in rats pretreated with MNNG and NaCl.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.4
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• pp.355-362
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• 2000

Neoplastic growth is characterized by alterations of oncogenes and antioncogenes. The interaction between activated oncogenes and functional deletion of antioncogene appears to be the driving force directing normal cells to uncontrolled growth resulting in tumor. In addition to those genes mentioned, other genes controlling the entry of cells into the cell cycle have recently been implicated in cancer development. The overexpression of the cyclin D1 gene, which has been mapped to 11q13, either by gene rearrangement or amplification has been noted in various malignant tumors. The product of the cyclin D1 gene forms a complex with cyclin-dependent protein kinases(CDK4) that governs a key transition in the cell cycle. The relationships between the overexpression of cyclin D1 assessed by immunihistochemistry and the amplification of the cyclin D1 gene by differential polymerase chain reaction(DPCR) using primers for dopamin D2 receptor gene in 13 cases of squamous cell carcinomas of the oral cavity have been studied. The semiquantitative assay of cyclin D1 amplification has been made by cyclin D1/dopamin D2 receptor(CD/DR) ratio. The results were as follows; 1. In the normal tissue and the tumor, the CD/DR ratios were 0.82 and 1.36 respectively. This implicates 1.65-fold amplification of cyclin D1 gene in tumor compared to that in normal tissue. 2. The tumor tissue which showed overexpression of cyclin D1 by immunohistochemistry revealed 2-fold amplification of cyclin D1 compared to the normal tissue. 3. The tumor tissue which showed mild expression of cyclin D1 by immunihistochemistry revealed 1.7-fold amplification of cyclin D compared to the normal tissue. 4. The cyclin D1 was overexpressed in the tumor tissue at the rate of 38%. Above results suggest that cyclin D1 has close correlation with the development of carcinoma in the oral cavity. But further studies were needed to elucidate the carcinogeneic mechanisms by comparative studies among cyclin D1, pRb and p53.

• Journal of the korean academy of Pediatric Dentistry
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• v.34 no.4
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• pp.679-684
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• 2007

Odontoma is the most common benign odontogenic tumors, and have been defined as mixed odontogenic tumor composed of epithelial and mesenchymal cells. Odontoma is believed to be hamartomatous rather than neoplastic in nature. The classification by WHO divides odontoma into 2 groups such as complex odontoma and compound odontoma. Compound odontoma comprises dental tissues, resembling the morphology of a tooth and has predilection for the anterior maxilla. In contrast, complex odontoma has unorganized mass, not resembling the normal tooth and has predilection for the posterior mandible. Odontoma is almost asymptomatic, so it is usually found on routine radiographic examination. Common presenting symptom is impacted or unerupted permanent teeth and retained primary teeth, but coexistent odontoma and congenital missing of permanent teeth is a very rare condition. The recommended treatment for an odontoma is conservative surgical excision, with care taken to remove the surrounding soft tissue. This report presents 2 patients with compound odontoma of the mandible who have congenital missing of the permanent teeth.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.4-9
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• 2001

Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.178-183
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• 2001

The nephrotic syndrome that occurs in the absence of renal vein thrombosis, amyloidosis, neoplastic infiltration of the kidneys is an unusual but a well recognized paraneoplastic syndrome. The most frequently reported neoplasms associated with nephrotic syndrome are Hodgkin's disease and various carcinomas. The most common renal lesions are membranous glomerulonephritis(MGN) associated with carcinomas and minimal change lesions associated with Hodgkin's disease. Approximately 40% to 45% of patients clinically manifest the MGN symptoms prior to the diagnosis of the tumor, 40% simultaneously with the tumor and the remaining 15% to 20% following the tumor. Therefore, evaluating the underlying malignancy in patients with MGN is important. Here we report a patient with squamous cell lung cancer, which was detected 12 months after a MGN had been diagnosed, with a review of the relevant literature.