• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.380-391
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• 1992

This study was designed to evaluate a direct method of $^{99m}Tc$ labeling using $\beta-mercaptoethanol$ as a reducing agent, and to investigate whether $^{99m}Tc$ labeled specific monoclonal antibody against carcinoembryonic antigen (CEA-92) can be used for the scintigraphic localization of human colon cancer xenograft. Purified CEA-92 IgG was fragmented into F $(ab')_2$ and then labeled with $^{99m}Tc$ by transchelation method using glucarate as a chelator. Labeling efficiency, immunological reactivity and in vitro stability of $^{99m}Tc$ CEA-92 F $(ab')_2$ were measured and then injected intravenously into nude mice bearing human colon cancer (SNU-C4). Scintigrams were obtained at 24 hour after injection. Then nude mice were sacrificed and the radioactivity was measured Labeling efficiency of injected $^{99m}Tc$ CEA-92 F $(ab')_2$, immunoreative fraction and in vitro stability at 24 hour of injected $^{99m}Tc$ CEA-92 F $(ab')_2$ was 45.2%, 32.8% and 57.4%, respectively. At 24 hour after injection, % ID/g in kidney (46.77) showed high uptake, but %ID/g in tumor (1.65) was significantly higher than spleen (0.69), muscle (0.16), intestine (0.45), stomach (0.75), heart (0.48) and blood (0.45). There was no significant difference between tumor and liver (1.81). Tumor contrast as quantitated by tumor to blood ratio of $^{99m}Tc$ CEA-92 F $(ab')_2$ was increased significantly (p<0.005) until 24 hours (3.70), and there was no statistical differece from tumor to blood ratio of I-131 CEA-92 F $(ab')_2$. The scintigram demonstrated localization of radioactivity over transplanted tumor, but significant background radioactivity was also noted over kidney and abdomen. It is concluded that CEA-92 F $(ab')_2$ can be labeled with $^{99m}Tc$ by a direct transchelation method using $\beta-mercaptoethanol$ as a reducing agent and $^{99m}Tc$ labeled CEA-92 F $(ab')_2$ can be used for the scintigraphic localization of human colon cancer xenograft in nude mice model.

• Molecules and Cells
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• v.37 no.8
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• pp.605-612
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• 2014

The p73 gene contains an extrinsic P1 promoter and an intrinsic P2 promoter, controlling the transcription of the pro-apoptotic TAp73 isoform and the anti-apoptotic ${\Delta}Np73$ isoform, respectively. The DNA methylation status of both promoters act equally in the epigenetic transcriptional regulation of their relevant isoforms. The aim of this study was to analyze the different effects of these p73 isoforms in 5-aza-2'-deoxycytidine (5-aza-dC)-induced apoptosis in breast cancer cells. We investigated the effects of the DNA demethylation agent, 5-aza-dC, on the T-47D breast cancer cell line, and evaluated the methylation status of the p73 promoters and expression of TAp73 and ${\Delta}Np73$. Furthermore, we assessed the expression of p53 and p73 isoforms in 5-aza-dC-treated T-47D cells and p53 knockout cells. 5-aza-dC induced significant anti-tumor effects in T-47D cells, including inhibition of cell viability, G1 phase arrest and apoptosis. This was associated with p73 promoter demethylation and a concomitant increase in TAp73 mRNA and protein expression. In contrast, the methylation status of promoter P2 was not associated with ${\Delta}Np73$ mRNA or protein levels. Furthermore, demethylation of P2 failed to inhibit the expression of ${\Delta}Np73$ with 5-aza-dC in the p53 knockdown cell model. Our study suggests that demethylation of the P1 and P2 promoters has opposite effects on the expression of p73 isoforms, namely up-regulation of TAp73 and down-regulation of ${\Delta}Np73$. We also demonstrate that p53 likely contributes to 5-aza-dC-induced ${\Delta}Np73$ transcriptional inactivation in breast cancer cells.

• Journal of Veterinary Clinics
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• v.26 no.6
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• pp.563-567
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• 2009

This study compared the instrument performance and tissue healing of a steel scalpel with a $CO_2$ laser in an animal uterine surgery model. Five Landrace and Yorkshire mixed breed pigs were used. Two symmetrical incisions were made in the uterine of each pig. One incision was made on the left side of the uterine horn using a steel scalpel, while the other incision was performed on the right side using a $CO_2$ laser with an 8W output power. Each instrument was evaluated clinically for speed, ease of incision, and extent of bleeding. An ovariohysterectomy was performed at 21 days after the surgical procedure for a histological examination. The scalpel was an easier instrument to use in the confines of the uterine tissue, compared with the laser. However, there is no significant difference between the two groups. The amount of bleeding was less in the laser group but the time of the incisions was shorter with the scalpel. Postoperative uterus adhesion in the $CO_2$ laser incisions was lower than the scalpel incisions. Scalpel incisions showed complete restoration of the epithelium and endometrial gland. On the other hand, the laser incisions showed incomplete restoration of the epithelium and endometrial gland. Although the scalpel produced less damage to the uterine tissue and was easier to handle than the $CO_2$ laser, it did not provide hemostasis that was helpful for use on highly vascular tissue. The $CO_2$ laser provided good hemostasis but delayed wound healing.

• Korean Journal of Community Nutrition
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• v.20 no.2
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• pp.129-140
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• 2015

Objectives: We examined the association between the adherence to dietary guidelines for breast cancer survivors and health-related quality of life in a cross-sectional study of Korean breast cancer survivors. Methods: A total of 157 women aged 21 to 79 years who had been diagnosed with stage I to III breast cancers according to the American Joint Committee on Cancer (AJCC) and had breast cancer surgery at least 6 months before the baseline were included. We used a Korean version of the Core 30 (C30) and Breast cancer 23 (BR23) module of the European Organization for Research and Treatment Cancer Quality of Life Questionnaire (EORTC-QLQ), both of which have been validated for Koreans. Participants were asked about their adherence to dietary guidelines for breast cancer survivors, suggested by the Korean breast cancer society, using a 5-point Likert scale. We summed dietary guideline adherence scores for each participant and calculated the least squares means of health-related quality of life according to dietary guideline adherence scores using the generalized linear model. Results: Breast cancer survivors who had higher adherence to dietary guidelines for breast cancer survivors had lower constipation scores than those with lower adherence (p for trend=0.01). When we stratified by the stage at diagnosis, this association was limited to those who had been diagnosed with stage II or III breast cancers. Also, sexual functioning scores increased significantly with increasing adherence scores of dietary guidelines among those with stage II or III breast cancers (p for trend < 0.001). However, among those who had been diagnosed with stage I, higher scores of dietary guidelines were associated with higher scores of pain (p for trend=0.03) and breast symptoms (p for trend=0.05). Conclusions: Our study suggested that the health-related quality of life levels of breast cancer survivors are associated with the adherence to dietary guidelines and may differ by the stage of the breast cancer.

• Korean Journal of Acupuncture
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• v.30 no.1
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• pp.56-63
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• 2013

Objectives : Effects of repetitive electroacupuncture(EA) on the pain behavior and activation of spinal glial cells were examined in the rat model of neuropathic pain. Methods : Twenty one adult male Sprague-Dawley rats were randomly assigned into 3 groups(control group, SP6 group, ST36+GB34 group). Neuropathic pain was induced by tight ligation of L5 spinal nerve. Mechanical and thermal hypersensitivity of hind paw were tested. Immunohistochemistry was performed in spinal cord L5/6 of all groups. EA was treated once in a day from the $5^{th}$ day after surgery. Results : EA treatments applied to ST36 and GB34 reduced significantly both of mechanical and thermal hypersensitivity after 3 times of treatment throughout the experiments. In the SP6 group, the analgesic effect was also shown after 7 times of treatment. Immunohistochemistry demonstrated inhibition of microglia and astrocyte activation in the spinal cord L5/6 dorsal horn in the ST36+GB34 group. Conclusions : The present results suggest that repetitive EA exert strong analgesic effect on neuropathic pain. These analgesic effects in neuropathic pain are associated with suppressing the activation of microglia and astrocyte.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• Journal of Acupuncture Research
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• v.23 no.5
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• pp.23-29
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• 2006

Objectives : The present study was conducted to evaluate the effects of automatically controlled rotating acupuncture (ACRA) on thermal allodynia in neuropathic pain rats, and to examine whether the endogenous opioid system mediates the effects of ACRA. Methods : For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, ACRA stimulation with 4 different stimulation conditions (i.e., angle and frequency of rotation: 90o+1Hz, 90o+1/4Hz, 360o+/1Hz, and 360o+1/4Hz) was delivered to the Zusanli (ST36) acupoint for 15 min. The behavioral signs of thermal allodynia were evaluated by the tail immersion test (i.e., immersing the tail in cold $(4^{\circ}C)$ or warm $(4^{\circ}C)$ water and measuring the latency to an abrupt tail movement) before and after the stimulation. In an additional set of experiments, we examined the effects of naloxone (opioid Results : ACRA stimulations under all of the conditions above significantly relieved thermal antagonist, 2mg/kg, i.p.) on the action of ACRA stimulation. allodynia. There is no difference in the anti-allodynic effects among the 4 stimulation conditions. In addition, the effect of ACRA on thermal allodynia was reversed by naloxone pretreatment. Conclusion : These results indicate that ACRA stimulations have relieving effects on thermal allodynia in neuropathic pain rats, irrespective of stimulation parameters, and that this is mediated by the endogenous opioid system.

• Journal of Acupuncture Research
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• v.30 no.3
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• pp.125-134
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• 2013

Objectives : We studied the effects of electro and laser acupuncture treatment with $GB_{39}$ and $GB_{34}$ on neuropathic pain in rats induced by tibial and sural nerve ligation. Methods : To produce the model of neuropathic pain, the tibial and sural nerves of rats were ligated by a 6-0 silk thread. Three days after the neuropathic surgery, only electro acupuncture(EA), electro acupuncture and 830 nm laser acupuncture(EA-LA-1), and electro acupuncture and 904 nm laser acupuncture(EA-LA-2) were treated with $GB_{39}$ and $GB_{34}$ twice a week for 8 weeks. We observed the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. We also observed c-fos and nocieptin on the central gray area in the midbrain of neuropathic rats. Results : As we observed the effect of mechanical allodynia, the EA and EA-LA-1 groups in 5 and 6 weeks and the EA-LA-2 group in 6 weeks increased significantly compared with the control group. As for the effect of c-fos activity in the central gray region, the EA, EA-LA-1, and EA-LA-2 groups decreased significantly compared with the control group. The EA-LA-2 group increased significantly compared with the control group as regards the effect of nociceptin activity in the central gray region. Conclusions : We noticed the synergic effect of electro and laser acupuncture treatment because the EA-LA-1 and EA-LA-2 groups had more controllable effect compared with the control group. This study can be used in clinical therapy for neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.5
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• pp.273-282
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• 2006

The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$, an activator of L-type $Ca^2+$ channels and cyclopiazonic acid $(10\;{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were also inhibited. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.2
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• pp.1292-1303
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• 2015

Jeju province is the highest area about obesity(1st), alcohol consumption(2nd) and male smoking(2nd) among sixteen Korean provinces by the report of Statistics Korea: 2013 community health survey. Therefore, it is assumed that the incidence rate of colon, liver, lung and breast cancer can be high. The purpose of this study is to test these cancer's incidence and mortality trends and compare comparability with national average. The Joinpoint regression model and permutation tests for identifying changes and parallelism in trend were used to test registered data at Jeju Regional Cancer Registry from 1999 to 2012. In male colorectal cancer, Average Age Percent Change(AAPC) of Age-Standardized incidence Rate(ASR) was 8.4% per year(p-value<.000) and the hypothesis of parallelism with Korean male average was rejected because of steep increasing of Jeju male patients' AAPC(p-value=.047). In male liver cancer, AAPC of ASR was -2.98 % per year(p-value<.000) and parallelism with Korean male average was rejected because of sluggish decreasing of Jeju(p-value=.026). In male lung cancer, the ASR parallelism with Korean male average was rejected(p-value=.009) because Jeju patients APC(4.37% per year) was increased during 2006~2012. This study demonstrates that AAPC and Trends of male colon, male lung and male liver were difference from national average. Further studies are needed to understand its causes.