• Journal of Life Science
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• v.14 no.1
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• pp.26-31
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• 2004

Redox factor-1 (Ref-1), known as a redox regulator, controls the DNA binding of AP-1 and is activated in HT29 colon cancer cells by hypoxia in vitro. REF-1 also increases tile DNA binding affinity of Hypoxia-inducible Factor-lalpha$ (HIF-lalpha$), HIF-like Factor (HLF) and early growth response-1 (Egr-1) which induce expression of the genes involved in angiogenesis, so that we speculate that REF-1 may play a role in hypoxia-induced angiogenesis. In this research we tried to detect novel proteins interacting with REF-1 using Yeast two-hybrid system using full-length REF-1 cDNA as bait. As result of such screening we detected 3 positive clones. DNA sequencing and GeneBank search revealed that one of the clones contained the same sequences as M.musculus cDNA for tioredoxin.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.336-342
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• 2008

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.495-500
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• 2005

The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.

• Journal of Chest Surgery
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• v.32 no.10
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• pp.910-915
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• 1999

Background: Positron emission tomography(PEFT) using fluorine-18 deoxyglucose(FDG), showing increased FDG uptake and retention in malignant cells, has been proven to be useful in differentiating malignant from benign tissues. We indertook the prospective study to compare the accuracy of the whole-body FDG PET with that of the conventional chest computed tomography(CT) for nodal staging of non-small-cell lung cancers(NSCLC). Material and Method: FDG PET and contrast enhanced CT were performed in 36 patients with potentially resectable NSCLC. Each Imaging study was evaluated independently, and nodal stations were localized according to the AJCC regional lymph nodes mapping system. Extensive lymph node dissection(1101 nodes) of ipsi- and contralateral mediastinal nodal stations was performed at thoracotomy and/or mediastinoscopy. Image findings were compared with the histopathologic staging results and were analyzed with the McNema test(p) and Kappa value(k). Result: The sensitivity, specificity, positive predictive value, and negative predictive value of CT for ipsilateral mediastinal nodal staging were 38%, 68%, 25%, 79%, and 61%, and those of PET were 88%, 71%, 47%, 95%, and 75%(p>0.05, K=0.29). When analyzed by individual nodal group(superior, aortopulmonary window, and inferior), the sensitivity, specificity, positive predictive value, and negative predictive value of CT were 27%, 82%, 22%, 85%, and 73%, and those of PET were 60%, 87%, 92%, and 82%(p<0.05, k=0.27). Conclusion: FDG PET in addition to CT appears to be superior to CT alone for mediastinal staging of non-small cell lung cancers.

• Archives of Reconstructive Microsurgery
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• v.18 no.1
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• pp.31-34
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• 2009

Purpose: Merkel cell carcinoma, also called neuroendocrine carcinoma, is a very rare type of skin cancer that develops as Merkel cells grow out of control. Merkel cell carcinoma is reported below 1% of whole skin neoplasms in the United States and is known that the 2-year survival rate is about 50~70%. The principles of treatment are wide excision of primary lesion with radiotherapy and/or chemotherapy that decrease the local recurrent rate. There has been no report of reconstruction with free flap after resection of Merkel cell carcinoma in Korea. Methods: We reconstructed the skin and soft tissue defect after wide excision of Merkel cell carcinoma with anterolateral thigh perforator free flap in two cases. No distant metastasis was found at the preoperative imaging work-up. In one case, preoperative chemotherapy was performed and the size of lesion was decreased. Results: There were no recurrence and significant complications. Functionally and aesthetically satisfactory results were obtained with reconstruction. Conclusion: Wide excision and reconstruction with anterolateral thigh perforator free flap for Merkel cell carcinoma patient is the first report in Korea. We regard this method as the treatment of choice in Merkel cell carcinoma.

• Korean Journal of Head & Neck Oncology
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• v.15 no.2
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• pp.222-225
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• 1999

Background and Objectives: Medullary thyroid carcinoma(MTC) is a rare tumor derived from the parafollicular C cells of the thyroid gland accounting for 5-10% of all thyroid malignancies. In Korea, there has been a few case report of medullary thyroid carcinoma(MTC) but their clinical analysis were not exactly studied. So, we made clinical study of 10 patients diagnosed as medullary thyroid carcinoma. Materials and Methods: We reviewed clinical data of 10 patients who were diagnosed as medullary thyroid carcinoma(MTC) from April 1973 to August 1998 at National Medical Center. Results: The incidence of MTC was 2.3% of all thyroid cancer and their mean age were 44.2 years old. Preoperative thyroid scan showed cold nodule in all patients and thyroid function test(TFT) was within normal range. Of the 10 patents, only 4 patients had diagnosis of MTC in preoperative fine needle aspiration biopsy. All the patients underwent total thyroidectomy with central neck dissection. Two patients with cervical lymph node metastasis underwent total thyroidectomy, central neck dissection and modified neck dissection. Two patients (20%) showed recurrence at the site of neck, lung, mediastinum, bone and liver. Conclusion: Most MTC is sporadic form and have peak incidence in the fifth decade and female preponderance. Preoperative fine needle aspiration biopsy is considered to be a clinically useful diagnostic method, but its accuracy is not considered as much high as others. Total thyroidectomy with central neck dissection may be an useful surgical modality in treating medullary thyroid carcinoma.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.4
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• pp.243-251
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• 2006

Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, however, the mechanisms of which are poorly understood. In the present study, it was investigated the further possible mechanisms by which dideoxytetrosynol A exerts its anti-proliferative action in cultured human leukemia cell line U937. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest of the cell cycle and apoptosis, which effects were associated with up-regulation of cyclin D1 and down-regulation of cyclin E without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression and activation of caspase-3 and caspase-9. Dideoxytetrosynol A decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, dideoxytetrosynol A treatment markedly inhibited the activity of telomerase, and the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by dideoxytetrosynol A treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxytetrosynol A.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.770-775
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• 2014

The green microalga of the genus Nannochloropsis (class Eustigmatophyceae) is a leading candidate for biofuel production due to its ability to accumulate high oil content (28.7% of cellular ash-free dry weight). We investigated the anti-inflammatory and anticancer activities of sterol-rich fraction from nannochloropsis oculata n-hexane (NOH) extract after saponification of the microalga. Among the fractions with n-hexane, chloroform and ethyl acetate, the n-hexane fraction showed the highest anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophage as well as anticancer activity against human leukemia HL-60 cells without the cytotoxity. And the sterol-rich fraction was obtained from the n-hexane fraction by open silica column under the gradient solvent condition with 100% hexane (1L), hexane : ethyl acetate (20 : 1, 10 : 1, 5 : 1, 1 : 1, v/v). Among the four fractions (NOH-1~4), especially NOH-1 contained the highest content of sterols. NOH1 showed the highest HL-60 (about 85%) and NO inhibitory activities at the concentration of $100{\mu}g/mL$. These results demonstrated that the sterol-rich fraction from N. oculata might be a useful candidate as anti-inflammatory and anticancer agents for anti-inflammatory and anticancer activity.

• The Journal of Korean Medicine
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• v.16 no.2 s.30
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• pp.365-385
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• 1995

In order to prove the antitumor effect of Wekyungtang(WKT) that was originated in Bigeubchunkeumyobang(備急千金要方), Wekyungtang with Houttuyniae Herba(WKT-I) and Wekyungtang with Oldenlandiae diffusae Herba(WKT-II) experimentally, the studies were done, We evaluated the cytotoxic activity against B16- Fo as well as the synergistic effects with anticancer drugs such as cyclophophamide (CPM), cisplatin(CPT) and 5-fluorouracil (5-FU) in vitro and measured body weight, survival time, hematological changes, changes of tissues in G57BL／6 implanted with B16-Fo. The results were obtained as follows: 1. In vitro cytotoxic effect against B16-Fo was shown in all groups as compared with control group, but the concentrations showing inhibitory growth rate below 55% of control was recognized in all concentrations of Wekyungtang(WKT) against B16-Fo and also concentration of $10^4$g／ml above in all group with cyclophophamide (CPM), concentration of $10^3$g／ml in Wekyungtang(WKT-l) with cisplatin(CPT) in synergistic effect, 2. In vivo body and tumor weight were significantly suppressed in all groups as compared with control group 3. The number of platelet, WBC, RBC were significantly increased in all groups, platelet aggregation was significantly increased in WKT-I and WKT-II as compared with control group. 4. In changes of tissues heavy infiltration oh cancer was shown in portal vein, pulmonary tissue, vein, peribronchiole, aveoli, while WKT-I was effective in antihepatic metastasis and WKT-II in pulmonary matastasis. From above results it was concluded that wekyungtang(WKT), wekyungtang with Houttuyniae Herba(WKT-I) and wekyungtang with Oldenlandiae diffusae Herba(WKT -II) had antitumor effect, and also wekyungtang combined with Houttuyniae Herba or Oldenlandiae diffusae Herba were more effective than wekyungtang only and also cyclophophamide (CPM), cisplatin(CPT) showed the more synergistic effect which suggests the necessity of continuous study on the mechanism of antitumor action of Houttuyniae Herba or Oldenlandiae diffusae Herba.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.1
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• pp.1-5
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• 2002

A fusion protein, consisting of a human epidermal growth factor (hEGF) as the recognition domain and human angiogenin as the toxin domain, can be used as a targeted therapeutic against breast cancer cells among others. The fusion protein was expressed as inclusion body in recombinant E. coli, and when the conventional, solution-phase refolding process was used the refolding yield was very low due to severe aggregation. It was probably because of the opposite electric charge at a neutral pH resulting from the vastly different pI values of each domain. The solid-phase refolding process that exploited the ionic interactions between ionic exchanger surface and the fusion protein was tried, but the adsorption yield was also very low, below $ 30\%$, regardless of the resins and pH conditions used. Therefore, to provide a higher ionic affinity toward the solid matrix, six lysine residues were tagged to the N-terminus of the hEGF domain. When heparin-Sepharose was used as the matrix, the adsorption capacity increased 2.5-3 times to about $88\%$. Besides the intrinsic affinity of angiogenin to heparin, the poly-lysine tag provided additional ionic affinity. And the subsequent refolding yield increased nearly 13-fold, from ca. $4.8\%$ in the conventional refolding of the untagged fusion protein to $63.6\%$. The process was highly reproducible. The refolded protein in the column eluate retained RNase bioactivity of angiogenin.