• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.85-85
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• 2003

This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Multidrug resistance(MDR) by tumor cells is a major obstacle to successful cancer chemotherapy. We report that the crude extracts of camellia flowers, leaves has a chemosensitizing effect that can reverse Pgp-mediated MDR by increasing the intracellular accumulation of drugs. The cytotoxic and chemosensitizing effects of MeOH extract from 12 spp. citrus fruits on the AML-2/D100 were determined using MTT assay. Chemosensitizing effects was screened in the presence of vincristine, a good substrate of Pgp. IC$\sub$50/ for extracts in AML-2/WT was found to be 65∼350$\mu\textrm{g}$/$m\ell$ whereas the range of its mean IC$\sub$50/ value in Pgp-overexpressing cells (AML-2/Dl00) in the presence of vincristine was 90∼400$\mu\textrm{g}$/$m\ell$. Of the extracts tested, mature leaf extract displayed the most potent chemosensitizing effect［IC$\sub$50/;100 $\mu\textrm{g}$/$m\ell$, CR;1.06, RF;2.97 in the presence of VCR］. This indicates that the toxicity (IC$\sub$50/;288.89$\mu\textrm{g}$/$m\ell$) of mature leaf extract is minimal at concentrations required for a complete reversal of the drug resistance. Also, this result indicates that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.165-171
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• 2007

Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

• Radiation Oncology Journal
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• v.2 no.1
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• pp.11-20
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• 1984

The renewed interest in the use of hyperthermia in cancer therapy is bases on radiobiological and clinical evidence indicated that there may be a significant therapeutic advantage with the use of heat alone or combined with radiation or chemotherapy, There are many methods for generating heat for localized tumor as like radiofrequency, microwave, electromagnetic induction and ultrasound. But it is very difficult to be even thermal dose distribution and stable output of power and then the detection of temperature in tumor is difficult to be precise with thermocouples and semiconductor sensors. We designed the microwave heating generator, dipole antenna applicators and autometic temperature controlled thermocouples for localized hyperthermia on skin and in cavities. 1. The microwave generator with 120 W, 2,450MHz magnetron could be heating up to $40^{\circ}C\~50^{\circ}C\;for\;1\~2$ hours in living tissues. 2. The thermal dose distribution in tissue with microwave was described $42^{\circ}C\~44^{\circ}C$ with in 3 cm depth and $2\~6cm$ diameter area. 3. Skin surface heating applicator with spiral 3 times wave length antenna radiated high Power of microwave. 4, Intracavitary heating applicator with dipole antenna with autometic control temperature sensor kept up continuously constant temperature in tissue. 5. For constant thermal distribution, applied two steps power with 10W microwave after $17\~20W$ during first 10 minutes. 6. The cooling rate by blood flew in living tissue was rised as $10\%$ then meats.

• Journal of Chest Surgery
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• v.25 no.6
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• pp.598-604
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• 1992

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and acounts for 6% to 15% of all cases of childhood cancer, Rhabdomyosarcoma in seventh most common form of childhood neoplasms, following acute leukemia, tumors of the central nervous system, lymphoma neuroblastoma, Wilm`s tumor, bone tumor. Rhabdomyosarcoma can arise anywhere in the body, but primary site in the thorax is relatively rare. We experienced a case of aveolar rhabdomyosarcoma arising from intercostal muscle, A 12 year-old woman was suffered from the intermittent left chest pain radiating to the scapular area and dyspnea, On physical examination, pulmonary friction rub was heard on the left upper lobe area. Qn adimission, the chest simple radiography revealed a 7 x 6, 5cm sized radio-opaque mass with pleural effusion in the superior mediastinum and the CT showed a well difined radio-opaque mass including the destructed 2nd rib and pleural effusion. The percutaneous tra-nsthoracic needle aspiration biopsy was likely to show blastoma. After the chemotherapy[vincristine, actinomycin-D, cyclophosphamde] was done to treat blastoma, the pleural effussion was subsided and the mass was slightly decreased by 4.5x 4. 5cm. For treatment and diagnosis, we performed en-bloc resection and the defected chest was reconstucted with Gortex patch. Grossly, the specimen was colored graysh-white and arised in between two ribs The microscopic findings showed that the tumor cells were small round with scant pinkish cytoplasm on the H-E stain and the tumor cell nests were grouped by reticulum fibers and showed alveolar pattern on the silver stain The electromicroscopic finding presented that the cytoplasm contained tangled fibrillar and flocculent materials. The histopathologic findings were compatable with laveolar rhabdomyosarcoma. She was discharged without any complication. After discharge, she has been treated with radiation theraphy and chemotheraphy, and not recurred untill last follow-up We report a case of alveolar rhabdomyosarcoma arising to intercostal muscle, developed in 12 year-old waman, with brief review of literatures.

• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.45-50
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• 2008

5-Fluorouracil (5-FU) is an antimetabolic of the pyrimidine derivatives that is used in chemotherapy for the treatment of several types of cancer. 5-FU have poor oral absorption and short biological half-time and strong side effects. Microneedle introduced to find a solution of problems. Microneedle device with roll was manufactured for transdermal delivery of various drugs. 5-FU was mixed in non-ionic surfactant such as tween 20 and tween 80. Camscope was used to analysis the permeation magnitude of treated skin by microneedle and trypan blue staining. The 5-FU solution with surfactant measured by ZETA-potential analysis system for stability of solution. The skin permeation rate of 5-FU determined by HPLC. We confirmed that cross treated skin was dyed more deeply than parallel treated skin through trypan blue staining. The results indicate that skin permeation rate of 5-FU was increased with the treatment types and treatment times.

• The Journal of Internal Korean Medicine
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• v.20 no.1
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• pp.133-142
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• 1999

To clarifiy the effects of Scolopendrae corpus(S-C) on turmor promotion in two-stage carcinogenesis in mice was investigated. In vivo system, S-C were seen to gave an inhibitory activity on TPA-induced mouse ear edema. In addition, the S-C were proved to have antitumor-promoting activity in two-stage mouse skin carcinogenesis induced by DMBA and two-stage mouse lung carcinogenesis induced by 4-NQO as a initiator plus TPA and glycerol as a promoter. Moreover, S-C significantly exhibited an cytolytic effect in $HepG_2$ cells and showed significant antitumor activity against Sarcoma-180 bearing mice by oral administration. These results suggest that S-C could be effective in adjuvant chemotherapy for human cancer.

• Journal of Chest Surgery
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• v.37 no.11
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• pp.929-932
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• 2004

The estimated relative incidence of primary pulmonary sarcoma to lung cancer is 0.4%. Furthermore, osteogenic sarcoma of the pulmonary artery is extremely rare. We report a case of a 63-year-old woman who visited our emergency room with the chief complaints of chest pain, dyspnea and dizziness. On echocardiography, right heart failure due to acute pulmonary artery embolism was diagnosed and we performed emergency operation. After opening the main pulmonary artery trunk, we found a mass attached to the arterial wall and massive thrombi around the mass. The mass was diagnosed as primary pulmonary artery osteosarcoma through postoperative evaluation. The patient received chemotherapy and radiotherapy. The patient is alive without specific symptoms 16 months postoperatively.

• Molecules and Cells
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• v.38 no.5
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• pp.416-425
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• 2015

NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2- upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-$G_0/G_1$ peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.

• Molecules and Cells
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• v.38 no.5
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• pp.396-401
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• 2015

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA. 3,4,5,5,7-Pentamethoxyflavone (PMF), a natural flavon extracted from Rutaceae plants, sensitized A549/CDDP to CDDP and substantially induced apoptosis compared with that of CDDP alone treated group, and this reversal effect decreased when Nrf2 was downregulated by siRNA. Mechanistically, PMF reduced Nrf2 expression leading to a reduction of Nrf2 downstream genes, and in contrast, this effect was decreased by blocking Nrf2 with siRNA. Taken together, these results demonstrated that PMF could be used as an effective adjuvant sensitizer to increase the efficacy of chemotherapeutic drugs by downregulating Nrf2 signaling pathway.

• Molecules and Cells
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• v.28 no.2
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• pp.119-124
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• 2009

Anti cancer agent 5-FU (Fluoro Uracil) is a prodrug that can be metabolized and then activated to interfere with RNA and DNA homeostasis. However, the majority of administered 5-FU is known to be catabolized in vivo in the liver where Dihydropyrimidine dehydrogenase (DPD) is abundantly expressed to degrade 5-FU. The biological factors that correlate with the response to 5-FU-based chemotherapy have been proposed to include uridine phosphorylase (UPP), thymidine phosphorylase (TPP), p53 and microsatellite instability. Among these, the expression of UPP is known to be controlled by cytokines such as $TNF-{\alpha}$, IL1 and $IFN-{\gamma}$. Our preliminary study using a DNA microarray technique showed that basic fibroblast growth factor (bFGF) markedly induced the expression of UPP1 at the transcription level. In the present study, we investigated whether bFGF could modulate the expression of UPP1 in osteo-lineage cells and examined the sensitivity of these cells to 5-FU mediated apoptosis.