• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.4
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• pp.292-296
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• 2004

The recombinant soluble human tumor necrosis factor-alpha (hTNF-$\alpha$) was expressed in a yeast Saccharomyces cerevisiae and its cytotoxicity was evaluated. A cDNA encoding hTNF-$\alpha$ was placed under the control of two different promoters: a glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter and a yeast hybrid ADH2-GPD promoter, consisting of alcohol dehydrogenase II (ADH2) and the GPD promoter. A Northern blot analysis revealed that, although variation in the expression level of hTNF-$\alpha$ existed among transformants, the higher expression was obtained with the GPD promoter. Expressed hTNF-$\alpha$ protein (rhTNF-$\alpha$) was successfully secreted into the culture medium, producing 2.5 mg per liter of culture filtrate, with no changes in cell growth. The bioassay for observing the cytotoxicity to the murine L929 fibroblast cell line, with serial dilution of rhTNF-$\alpha$, indicated that the secreted rhTNF-$\alpha$ was bioactive and its dose-response was improved eight to ten times over that of the E. coli-derived rhTNF-$\alpha$.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.1
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• pp.1-9
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• 2011

Purpose: Tumor associated angiogenesis and/or lymphangiogenesis are known to be linked by VEGFR signaling pathways. These processes are regulated by several growth factors including VEGFR-2, VEGFR-3. E7080 is an orally active inhibitor of multiple tyrosine kinases including VEGFR-2, 3. Therefore, it was proposed that E7080 may inhibit angiogenesis and lymphangiogenesis. The aim of this study was to determine the effect of E7080 in a nude mouse model of OSCC. Methods: KB cells were xenografted into the submucosal tissue of the mouth floor of athymic mice. Seven days after the xenograft, the mice were randomized into 2 groups. E7080 were administered orally to the experimental group once per day. The mice were sacrificed 3 weeks after the treatment. The tumors were examined histopathologically. Immunohistochemical assays with anti- VEGF-C, VEGFR-2, VEGFR-3, phosphorylated VEGFR-2/3 (pVEGFR-2/3), and D2-40 antibodies were then performed. Results: The transplantation of human OSCC tumor cells into the mouth floor resulted in the formation of orthotopic tumors. The experimental (E7080 treatment) group showed a slowly increased tumor volume. Moreover, immunohistochemical staining demonstrated higher levels of VEGF-C, VEGFR-2, VEGFR-3, pVEGFR-2/3 and D2-40 expression in the control group than in the experimental group. Conclusion: These results suggest that E7080 may provide therapeutic benefits in OSCC.

• The Journal of the Korean bone and joint tumor society
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• v.12 no.1
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• pp.9-14
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• 2006

Purpose: The proximal tibial sarcoma patients, especially in their growing ages have problems of reconstruction. This study is to devise a methodology which can circumvent this limitations. Materials and Methods: Four cases of proximal tibial osteosarcoma underwent hemiarthroplasty. The mean age was 13 years (11~15) with a mean follow-up of 64 months (47~89). The procedure consists of ultrahigh molecular weight polyethylene (UHMWPE) liner as an substitute for the joint surface and this piece was fixed to the remaining tibial bone stock with Ender nail and bone cement. Results: Final functional score was 23.5 (78.3% of control) by MSTS criteria. All the cases showed stable joint without pain. Hemiarthroplasty related complications were absent. By saving the femoral physis, expected leg length discrepancy could be minimized by this procedure. Conclusions: Hemiarthroplasty of proximal tibia can be an option in pediatric sarcoma patients.

• Journal of Korean Neurosurgical Society
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• v.54 no.3
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• pp.175-182
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• 2013

Objective : Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. Methods : Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. Results : There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. Conclusion : Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.30-47
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• 2006

Objective : The present study is aimed to elucidate the effects of Cirsium japonicum var. ussuriense on immunomodulation and the potential as an herbal remedy for cancer treatment. Method : It was performed through measurement of effects Cirsium japonicum var. ussuriense extract (CJE) on NO production, NK cell cytotoxicity and cytokine gene expressions related with macrophage and NK cell activity. Result : 1. CJE did not show any direct cytotoxic effects on 7250, HT1080, Hep G2 and CT-26 cells. 2. CJE activated macrophages partially to product NO and up-regulated gene expressions for iNOS in RAW 264.7 cells. 3. CJE promoted cytotoxicity of NK cells against YAC-1 cells at higher concentration than 200 ${\mu}g/ml$. 4. CJE up-regulated gene expressions for $IL-1{\beta}$, IL-2, iNOS, $IFN-{\gamma}$ and $TNF-{\alpha}$ in mice splenocytes.　５. CJE inhibited lung tumor metastasis induced by CT-26 cell transplantation compared with the control group.　Conclusion : It could be concluded that CJE is an effective herbal drug for immune modulating and anti-cancer treatment by promoting activity of macrophages and NK cells.

• BMB Reports
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• v.34 no.3
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• pp.206-211
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• 2001

Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and the growth of several primary tumors. However, the opinions on the activity of endostatin derivatives deleted N- or C- terminal are still controversial. In this regard, we produced mouse endostatin and its derivatives in the prokaryotic system, and studied their anti-tumor activity. The [$^3H$]-thymidine incorporation assay demonstrated that N-terminal deleted mouse endostatin, and a C- and N-terminal deleted mutant, effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs). The biological activity of endostatin was also shown by its in vivo anti-angiogenic ability on the chorioallantoic membrane (CAM) of a chick embryo. Treatment of $200\;{\mu}g$ of mouse endostatin, or N-terminal deleted mouse endostatin, inhibited capillary formation of CAM 45 to 71%, which is comparative to a 80% effect of positive control, $1\;{\mu}g$ of retinoic acid. An in vivo mouse tumor growth assay showed that N-terminal deleted mouse endostatin, and the N-/C-terminal deleted mutant, significantly repressed the growth of B16F10 melanoma cells in mice as did the full-length mouse endostatin. According to these results, N-and N-/C-terminal deleted mouse endostatins are the potent inhibitors of tumor growth and angiogenesis.

• Korean Journal of Head & Neck Oncology
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• v.16 no.2
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• pp.161-166
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• 2000

Objective: The nm23 gene has been identified as a potential metastasis suppressor gene in various human neoplasms. Both Bcl-2, which promotes cell survival, and Bax, which promotes cell death, have been considered as major factors in controlling the apoptotic pathway. This study was carried out to determine whether these markers are useful in distinguishing potential intrinsic differences in tumor virulence of papillary thyroid cancers. Material and Method: The expressions of nm23, Bcl-2 and Bax have been evaluated using immunohistochemical techniques in 100 pure papillary thyroid cancers and 20 metastatic lymphnodes. The intensity of immnunoreactivity was graded on arbitrary four point scale(grade 0 or 1 : negative reactivity, grade 2 or 3 positive reactivity). The immunoreactivities were analyzed in relation to TNM atage, AMES score, local recurrence and distant metastasis, and that of metastatic LNs was compared with the tumors. Results: The expression of Bcl-2 and bax did not show any statistical differences by TNM stage, AMES score, recurrence, distant metastasis and also between the tumor and metastatic LN. However, the nm23 showed higher expression of Ki67 in distant metastasis than in control group and in metastatic LNs than in the tumors(p<0.05). Conclusion: Although the expression of Bcl-2 and Bax protein showed no correlation with clinical parameters representing tumor virulence, the nm23 expression could be an useful prognostic factor, especially in predicting nodal or distant metastasis in papillary thyroid cancer.

• Journal of Korean Neurosurgical Society
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• v.45 no.3
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• pp.157-163
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• 2009

Objective : In recent years, CyberKnife has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing CyberKnife and the complications of this procedure are reviewed. Methods : Twenty-six patients with pituitary adenomas received stereotactic radiosurgery with the CyberKnife (CKRS). The follow-up periods ranged from 7 months to 47 months (mean$\pm$SD : $30{\pm}12.7$ months). The patients consisted of 17 with non-functioning adenomas, 3 with prolactinomas and 6 with acromegaly. The change in the tumor volume, visual acuity, hormonal function, and complications by this therapy were analyzed in each case. Results : The tumor control rate was 92.3%. Hormonal function was improved in all of the 9 (100%) functioning adenomas. Hormonal normalization was observed in 4 of the 9 (44%) patients with a mean duration of 16 months. In two patients (7.6%), visual acuity worsened due to cystic enlargement of the tumor after CKRS. No other complications were observed. Conclusion : CyberKnife is considered safe and effective in selected patients with pituitary adenomas. However, longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.27 no.1
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• pp.107-122
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• 1997

Radiation sensitivity data was generated for two human cancer cell lines(KB, RPMI 2650) and human primary gingival fibroblast was tested three times using a viable cell number counting with a hemocytometer, MTT(3-[4,5-Dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide) assay, and LDH(Lactate dehydrogenase) assay. Single irradiation of 2, 4, 6, 10, 15, 20Gy were applied to the tumor cell lines and the primary cultured gingival fibroblast The two fractions of 4Gy and 10Gy were seperated with a 4 hour time interval. The irradiation was done with 241.5cGy/min dose rate using /sup 137/Cs MK cell irradiator at room temperature. The obtained results were as followed : 1. There was significantly different viable cell numbers as the amount of radiation dose on the tested cells were cell number counted with a hemocytometer. In fractions, there were more viable cells remaining. 2. Phase-contrast microscopically, radiation-induced morphologic changes were pronounced on the tumor cells, however, almost no differences on the gingival fibroblast. 3. There was significantly different absorbance at 2Gy on RPMI 2600, 4Gy on KB and GF in MTT assay. In fractions, the absorbance was significantly higher on KB. 4. The level of extracellular LDH activity in the experimental group was significantly higher in the 2-4Gy than the control group. 5. The total level of extracellular and intracellular LDH activity was decreased as increased amounts of radiation dose was applied.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9071-9075
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• 2014

Background: microRNAs are small non-coding RNA that control gene expression by mRNA degradation or translational inhibition. These molecules are known to play essential roles in many biological and physiological processes. miR-205 may be differentially expressed in head and neck cancers; however, there are conflicting data and localization of expression has yet to be determined. Materials and Methods: miR-205 expression was investigated in 48 cases of inflammatory, benign and malignant tumor tissue array of the neck, oronasopharynx, larynx and salivary glands by Locked Nucleic Acid in situ hybridization (LNA-ISH) technology. Results: miR-205 expression was significantly differentially expressed across all of the inflammatory, benign and malignant tumor tissues of the neck. A significant increase in miR-205 staining intensity (p<0.05) was observed from inflammation to benign and malignant tumors in head and neck tissue array, suggesting that miR-205 could be a biomarker to differentiate between cancer and non-cancer tissues. Conclusions: LNA-ISH revealed that miR-205 exhibited significant differential cytoplasmic and nuclear staining among inflammation, benign and malignant tumors of head and neck. miR-205 was not only exclusively expressed in squamous epithelial malignancy. This study offers information and a basis for a comprehensive study of the role of miR-205 that may be useful as a biomarker and/or therapeutic target in head and neck tumors.