• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.403-411
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• 2009

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

• Journal of Pharmacopuncture
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• v.7 no.2
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• pp.65-73
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• 2004

Objective : This study was to review on the prostate disease-related studies with Acupuncture therapy in renowned medical internet site of PubMed, and to make master plan of the study, especially, on Bee Venom Acupuncture(BVA) of Prostate disease and then to devise the idealistic therapeutic ways of it. Method : We made the internet search with the key words of bee venom(bee venom therapy, apitoxin, apitherapy, bee sting, bee sting therapy), acupuncture, prostate, prostatitis, prostrate cancer in Pubmed, from June 1st to July 1st,2004. Results : 1.25 papers were found in 19 publised jounals. of which two named'Urology'and Prostate' had three papars, two called 'JUrology' and 'Cancer Immunol Immunother' had two papers, and the others had a paper respectively. 2. In the classification by papers' types, Review papers were 8 and Original were 17 where there were 5 clinical trials, 11 experimental studies and 1 epidemiologic paper. Of 5 clinical trials, 2 belonged to Randomized Control Study, and of 11 experimental studies, 4 belonged to in vitro and 7 belonged to in vivo with in viro studies, and 1 epidemeologic belonged to meta-analysis. 3. In the classification by prostate diseases, 4 were about prostatitis, 3 were about prostate related symptoms, 16 were about prostate cancer, and two were about the others. 4. In the classification by applied treatment methods, 5 were related with Acupuncture, 10 were related with BVA(Bee Venom, Bee), and 10 were related with the others. Of 5 related with Acupuncture, 3 used general acupuncture, 1 used electrical acupuncture, and 1 used general acupuncture and electrical acupuncture at the same time. 5. In 2 RCTs of Clinical trials, Control group was set up to the group using different compatible treatment method or using meridians not related with treating prostate disease. Single or double blind methods couldn't be found. 6. In the clinical trials, IPSS, NIH, CPSI or subjective global assessment were used as the Index of Evaluation. 7. The Leg Greater Yang Bladder Meridian(B), The Leg Lesser Um Kidney Meridian(K) and Conception Vessel Meridian(CV) were used as major meridians, and B10(Taejo, Dazhu), B23(Shinsu, Shenshu), B28(Panggwangsu, Pangguangshu), B35(Hoeyang, Huiyang), B39(Wiyang, Weiyang), B40(Wijung, Weizhong), B54(chilbyon, Zhibian), K1(Yongchon, Yongquan), K10(Umgok, Yingu), CV3(Chungguk, Zhongji), CV4(Kwanwon, Guanyuan),S6(Hyopko, Jiache) were used as acupoints. Electrical acupuncture(EA) was considered to be more important and CV3(Chungguk, Zhongji), CV4(Kwanwon, Guanyuan) were mainly selected as EA applied acupoints. 8. It is mostly said that Acupuncture appeared to be a safe, effective, and durable treatment alternative in improving symptoms of patients with prostate diseases, refractory to conventional medicine. A larger controlled study was required to confirm these encouraging initial results. Conclusion : Papers about BVA of Prostate cancer or Prostatitis were not found, and low permeability of Prostate is concerned, BVA with the anti-inflammatory and anti-cancer effect can be adopted as a new alternatives of Prostate disease treatment, so it is thought that Study of how to make access to prostate, animal experiment including in vivo and in vitro and more clinical trials with using acupoints on related meridian should be followed.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.314-319
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• 2007

The effects of common variants of CYP1A2 gene (CYP1A2$^*$1C and CYP1A2$^*$1F) on the CYP1A2 activity and inducibility were controversial. The aim of the present study is to investigate the effects of CYP1A2$^*$1C and CYP1A2$^*$1F on the activity of CYP1A2 determined by urinary caffeine metabolite ratio in Koreans. As might be expected, there was large inter-individual variation (16-folds) of CYP1A2 activity ranged from 2.41 to 39.58. The mean CYP1A2 activity of smokers was significantly higher than that of non-smokers. The frequencies of CYP1A2$^*$1C (-3858A) and $^*$1F (-164A) alleles were 0.219 and 0.646, respectively. The effect of CYP1A2$^*$1C on the CYP1A2 activity was not significant. However, the CYP1A2 activity of subjects with AA genotype for CYP1A2$^*$1F allele was significantly lower than that of non-AA genotypes (CC, or CA). Interestingly, the significant effect of CYP1A2$^*$1F allele on CYP1A2 activity was not observed in nonsmokers. Our results suggest that CYP1A2$^*$1F allele rather than CYP1A2$^*$1C allele significantly influences on the inducibility of CYP1A2 in Koreans. Owing to small sample size of our study, further studies should be conducted to reveal the inter-ethnic difference or the gene-environmental interaction.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.215-221
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• 2007

Neuronal cell toxicity induced by decreased nitric oxide (NO) production may be caused by modulation of constitutive neuronal NO synthase (nNOS). We used lead acetate ($Pb^{2+}$) to modulate physiological NO release and the related pathways of protein kinases like PKC, CaM-KII, and PKA in CATH.a cells, a dopaminergic cell line that has constitutive nNOS activity. In the cells treated with $Pb^{2+}$, cell viability and modulation (phosphorylation) levels of nNOS were determined by MTT assay and Western blot analysis, respectively. nNOS reductase activity (cytochrome c) was also assessed to compare the phosphorylation site-specific nNOS activity. nNOS activity was also determined by NADPH consumption rates. $Pb^{2+}$ treatment alone increased the phosphorylation of nNOS with decreased reductase activity. The phosphorylation levels increased markedly with decreased nNOS reductase activity, when $Pb^{2+}$ was combined with inhibitors for two (PKC and CaM-KII) or three (PKA, PKC and CaM-KII) protein kinases. Interestingly, when the cells were exposed to $Pb^{2+}$ plus PKC or CaM-KII inhibitor, the nNOS was phosphorylated strongly with the lowest activity. However, the levels of phosphorylated nNOS following $Pb^{2+}$ treatment decreased significantly after combined treatment with the PKA inhibitor, and $Pb^{2+}$-induced suppression of reductase activity did not occur. These results demonstrate that physiological NO release in the neuronal cells exposed to $Pb^{2+}$ can be decreased by PKA-mediated nNOS phosphorylation that may be caused by interactions with PKC and/or CaM-KII.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.260-265
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• 2001

Transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) is a multipotent growth factor affecting development, homeostasis and tissue repair. Many kinds of malignant tissues were reported to overexpress transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) gene. However, a little work has been done on the circulating $TGF-{\beta}1$ and the association of $TGF-{\beta}1$ with progression in patients with malignant tumors. In this study, we measured the plasma level of $TGF-{\beta}1$ in gastric cancer and prostate cancer patients and evaluated the utility of plasma $TGF-{\beta}1$ as a possible tumor marker. We used Enzyme-linked immunosorbent assay (ELISA) system in order to measure plasma $TGF-{\beta}1$ level in 134 gastric cancer patients, 50 prostate cancer patients and 290 normal controls. And the tumor marker, carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), was compared with $TGF-{\beta}1$ in the aspects of sensitivity and specificity. The mean plasma $TGF-{\beta}1$ levels were $1.219{\pm}0.834$ (0.272-5.772) ng/mL in normal controls, $5.964{\pm}3.218$ (0.845-18.124) ng/mL in gastric cancer and $4.140{\pm}2.345$ (1.108-13.302) ng/mL in prostate cancer. In gastric cancer patients difference in plasma $TGF-{\beta}1$ level was not detected according to cancer stage. In comparison with other tumor marker (CEA, PSA) $TGF-{\beta}1$ is more potent in sensitivity. These results indicate that the plasma $TGF-{\beta}1$ level can be a potent tumor marker in gastric cancer and prostate cancer.

• IMMUNE NETWORK
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• v.12 no.1
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• pp.33-39
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• 2012

Background: Therapeutic approaches using monoclonal antibodies (mAbs) against complement regulatory proteins (CRPs:i.e.,CD46,CD55 and CD59) have been reported for adjuvant cancer therapy. In this study, we generated a recombinant 1E8 single-chain anti-CD59 antibody (scFv-Fc) and tested anti-cancer effect.by using complement dependent cytotoxicity (CDC). Methods: We isolated mRNA from 1E8 hybridoma cells and amplified the variable regions of the heavy chain (VH) and light chain (VL) genes using reversetranscriptase polymerase chain reaction (RT-PCR). Using a linker, the amplified sequences for the heavy and light chains were each connected to the sequence for a single polypeptide chain that was designed to be expressed. The VL and VH fragments were cloned into the pOptiVEC-TOPO vector that contained the human CH2-CH3 fragment. Then, 293T cells were transfected with the 1E8 single-chain Fv-Fc (scFv-Fc) constructs. CD59 expression was evaluated in the prostate cancer cell lines using flow cytometry. The enhancement of CDC effect by mouse 1E8 and 1E8 scFv-Fc were evaluated using a cytotoxicity assay. Results: The scFv-Fc constructs were expressed by the transfected 293T cells and secreted into the culture medium. The immunoreactivity of the secreted scFv-Fc construct was similar to that of the mouse 1E8 for CCRF-CEM cells. The molecular masses of 1E8 scFv-Fc were about 120 kDa and 55 kDa under reducing and non-reducing conditions, respectively. The DNA sequence of 1E8 scFv-Fc was obtained and presented. CD59 was highly expressed by the prostate cancer cell line. The recombinant 1E8 scFv-Fc mAb revealed significantly enhanced CDC effect similar with mouse 1E8 for prostate cancer cells. Conclusion: A 1E8 scFv-Fc construct for adjuvant cancer therapy was developed.

• Childhood Kidney Diseases
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• v.5 no.1
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• pp.15-21
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• 2001

Purpose : Urinary tract infections (UTIs) of children require prompt and correct diagnosis and treatment to reduce the risk of renal damage. As a first step to improve the outcome of UTI in Korea, we investigated the practical variations in the methods of diagnosis, treatment, and evaluation of children with UTI and UTI prevention. Method :A questionnaire related to the individual policy on UTI diagnosis. treatment, imaging test, and prevention was submitted to 26 experts. Result Majority of the experts used bag-collected urine specimen for infants and mid-stream urine specimen for children for urinary culture. With a negative result of culture study, they diagnosed UTI when there was pyuria, positive results of the nitrite test, or bacteriuria. 80 $\%$ of experts prescribed prophylactic antibiotics after upper tract UTI. Operative treatment of vesicoureteral reflux (VUR) was indicated for children older than one or two years old with high-grade VUR, refractory breakthrough infections, or recurrent UTIs. Most of them performed kidney ultrasonography on the diagnosis of UTI and more than half of them evaluated children treated of UTI with vesicocystourethrogram and/or DMSA scintigraphy. Majority did not recommend circumcision. Half of the experts were screening siblings of VUR patients. Conclusion : Considering the variations exposed through this study systematic guidelines for management of children with UTI in Korean would be necessary. (J. Korean Soc Pediatr Nephrol 5 : 15-21, 2001)

• Childhood Kidney Diseases
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• v.13 no.1
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• pp.26-32
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• 2009

Purpose : The increasing use of ultrasonography has allowed for an increase in the of the detection of congenital hydronephrosis, and the clinical outcomes of congenital hydronephrosis are widely varied. In this study, the necessity of voiding cystourethrography in neonate with hydronephrosis to rule out vesicoureteral reflux (VUR) was evaluated. Methods : Between January 2004 and December 2007, we reviewed the medical record of 157 childrens with congenital hydronephrosis detected within 1 month of age. The severity of hydronephrosis was graded by SFU (Society of Fetal Urology) system, and anterior posterior pelvic diameter (APPD). We evaluated the relationship between severity of hydronephrosis and incidence of VUR by using SPSS windows version 16.0. A P-value<0.05 is considered to be statistically significant. Results : Total renal unit number was 254, and 20(7.8%) renal units had VUR. We did not find any relationship between hydronephrosis grade the presence of VUR grade (P>0.05). In addition, there was no statistical significance between APPD, laterality of hydronephrosis and VUR incidence. However, renal units with VUR had lower spontaneous resolution rate (P<0.05), compared to renal units without VUR. Conclusion : In this study, there was no statistical significance between the severity of hydronephrosis and presence of VUR. Therefore, voiding cystourethrogram is recommended for all children with hydronephrosis to rule out VUR, regardless of the severity of hydronephrosis.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.11
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• pp.314-323
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• 2019

This study examined the factors affecting clinical practice adaptation to provide basic data for the improvement of clinical practice adaptation for the first year of clinical practice. The subjects were 153 nursing students and medical students in G-do. Data were collected from April 1 to April 30, 2019, and analyzed using a t-test, ANOVA, Pearson correlation coefficient, and multiple regression using IBM SPSS WIN/21.0. The mean of college adjustment, character, interpersonal competence, communicative competence, and clinical practice adaptation was 3.37 points, 3.82, 3.61, 3.56, and 3.54, respectively. Clinical practice adaptation was related to college adjustment, character, interpersonal competence, and communicative competence (p<.001). The most influential factor in clinical practice was interpersonal competence (β=.502, p<.001), followed by department adaptation (β=-.215, p<.001) and college adjustment (β=.174, p=.010), respectively. The explanatory power was 41.1% (F=34.11, p<.001). Therefore, a way to improve interpersonal competence is needed to advance clinical practice adaptation. In the character building program for adjustment to college life, systematic education is needed, including the opportunity to think about and understand oneself, continuous meeting to understand and accept others. In addition, repeated communication training to improve interpersonal competence is needed.