• The Korean Journal of Nuclear Medicine Technology
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• v.12 no.1
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• pp.49-56
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• 2008

Purpose: Whole body imaging with radioiodine can detect functioning metastases. Non-physiologic I-131 uptake detected on images usually is interpreted as suggesting functioning thyroid metastases. However, extra-thyroidal I-131 accumulation does not always imply thyroid cancer metastases and has been reported in many circumstances. In order to avoid unnecessary therapeutic interventions it is important to distinguish false-positive sites of I-131 localization. We study here to remove false-positive sites around esophagus region on I-131 whole body imaging in patients who were administrated thyroidectomy. Materials and Methods: From April to August in 2007, we had the patients who had visited our department after they received thyroidectomy due to thyroid cancer. They were given I-131, and performed radioiodine body scan after 41 to 50 hours. Patients were whole-body-scanned for the speed of 8 cm per minute. After that, we took anterior and posterior static images around the patients' neck measured by 300 thousand counts per image. We selected 44 patients who had hot spots around neck region, we divided the patients into two groups. One group was given 0.5 L of water and the other group was given 0.5 L of water with 1 g of Vitamin C dissolved. The patients were asked to drink the fluid for one minute in sitting position and after that, we measured 300 kilo counts per image again. We compared prior anterior, posterior static images with anterior, posterior images after the patients had water or water that Vitamin C resolved. Results: In using water, both observer 1 and 2 interpreted 6 patients were washed out. In the water with Vitamin C resolved, observer 1 and 2 interpreted 9 and 8 patients were washed out. Observer 1 and 2 interpreted 6 and 5 patients had 'indeterminate' when they used water. Both observer 1 and 2 interpreted 6 patients had 'indeterminate' when they used water with Vitamin C resolved. When they used water, observer 1 interpreted 10 patients had 'unchanged' and observer 2 interpreted 11 patients had 'unchanged'. Differently, when they used water with vitamin C resolved, observer1 had 8 patients having 'unchanged'and observer 2 had 9. Conclusion: As a result, by making patients drink 0.5 liter of water which has vitamin C resolved helped getting rid of false-positive sites in esophagus. Therefore, based on this study, we believe that drinking water with vitamin C dissolved is very in terms of reducing false-positive hot spot around the esophagus for the iodine-131 whole body scan.

• Journal of Life Science
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• v.19 no.1
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• pp.123-128
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• 2009

Production of highly valuable immunotherapeutic proteins such as monoclonal antibodies and vaccines using plant biotechnology and genetic engineering has been studied as a popular research field. Plant expression system for mass production of such useful recombinant therapeutic proteins has several advantages over other existing expression systems with economical and safety issues. Immunotherapy of multiple monoclonal antibodies, which can recognize multiple targeting including specific proteins and their glycans highly expressed on the surface of cancer cells, can be an efficient treatment compared to a single targeting immunotherapy using a single antibody. In this study, we have established plant production system to express two different targeting monoclonal antibodies in a single transgenic plant through crossing fertilization between two different transgenic plants expressing anti-colorectal cancer mAbCO17-1A and anti-breast cancer mAbBR55, respectively. The F1 seedlings were obtained cross fertilization between the two transgenic parental plants. The presence, transcription, and protein expression of heavy chain (HC) and light chain (LC) genes of both mAbs in the seedlings were investigated by PCR, RT-PCR, and immunoblot analyses, respectively. Among all the seedlings, some seedlings did not carry or transcribe the HC and LC genes of both mAbs. Thus, the seedlings with presence and transcription of HC and LC genes of both mAbs were selected, and the selected seedlings were confirmed to have relatively stronger density of HC and LC protein bands compared to the transgenic plant expressing only each mAb. These results indicate that the F1 seedling plant with carrying both mAb genes was established. Taken together, plant crossing fertilization can be applied to generate an efficient production system expressing multiple monoclonal antibodies for immunotherapy in a single plant.

• Journal of Life Science
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• v.24 no.12
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• pp.1339-1344
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• 2014

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

• Journal of Life Science
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• v.29 no.12
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• pp.1305-1313
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• 2019

Licochalcone (LC), isolated from the roots of Glycyrrhiza inflata has multiple pharmacological effects including anti-inflammatory and anti-tumor activities. To date, Licochalcone C (LCC) has induced apoptosis and inhibited cell proliferation in oral and bladder cancer cells, but lung cancer has not yet been studied. In addition, no study reported LCC-induced autophagy in cancer until now. The present study was designed to investigate the effect of LCC on gefitinib-sensitive and -resistant lung cancer cells and elucidate the mechanism of its action. The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay data showed that LCC significantly inhibited cell viability in non-small cell lung cancer (NSCLC) HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) cell lines. Interestingly, Annexin V/7-aminoactinomycin D double staining and cell cycle analysis showed an apoptosis rate within about 20% at the highest concentration of LCC. LCC induced G2/M arrest by reducing the expression of the cell cycle G2/M related proteins cyclin B1 and cdc2 in NSCLC cell lines. Treatment of LCC also induced autophagy by increasing the expression of the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) and the protein autophagy-related gene 5 involved in the autophagy process. In addition, LCC increased the production of reactive oxygen species (ROS), and the cell viability was partially restored by treatment with the ROS inhibitor N-acetyl-L-cysteine. In western blotting analysis, the expression of cdc2 was increased and LC3 was decreased by the simultaneous treatment of NAC and LCC. These results indicate that LCC may contribute to anti-tumor effects by inducing ROS-dependent G2/M arrest and autophagy in NSCLC. In conclusion, LCC treatment may be useful as a potential therapeutic agent against NSCLC.

• Journal of Food Hygiene and Safety
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• v.31 no.1
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• pp.51-58
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• 2016

This research examined the effects of Compositae extract on the inhibition of proliferation and apoptosis in human breast and human gastric cancer cells. Compositae extracts which is used in the experiment are Taraxacum coreanum (TC), Youngia sonchifolia (YS) and Ixeris dentata (ID). The proliferation of SK-BR-3, MDA-MB-231 and AGS cells were investigated by MTT assay. ID and YS extracts inhibited proliferation of SK-BR-3, MDA-MB-231 and AGS cells in a dose-dependent manner, but TC have barely affected. In addition, the most effective extract was ID. To assess the apoptosis of ID extract, the nuclei of human cancer cells were stained with DAPI solution respectively. Chromatin condensation, indicated apoptosis, was increased in a dose-dependent manner. We investigated change of ID extract-induced apoptosis proteins on human cancer cells by western blot analysis. The level of Bcl-2 decreased, whereas the level of Bax, cleaved-PARP increased in dose-dependent manner compared with non-treatment. Also Bax/Bcl-2 ratio, which is used in clinical indicator of apoptosis, was increased at ID extract treatment group compared with non-treatment. Moreover the Bax/Bcl-2 ratio of MDA-MB-231 cell was significantly increased as against SK-BR-3, AGS cells. These results indicated that ID extract have anti-proliferation effect better than YS or TC, and induced apoptosis in human breast cancer MDA-MB-231 cell better than human breast cancer SK-BR-3 cell, human gastric cancer. Even if further research is needed, ID can be developed as a chemopreventive or therapeutic agent of breast cancer.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.33-42
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• 2004

Purpose : Children with nephrotic syndrome(NS) are under high risk for metabolic bone disease(MBD) as a complication of long-term glucocorticoid therapy. We prospectively evaluated the effect of oral bisphosphonate(alendronate) therapy in children with NS, which has proven efficacy in adult patients with glucocorticoid induced MBD. Methods : Among 58 children with NS, aged 5 to 8 years and haying a disease duration of more than 2 years, 30(51.7%) were enrolled to meet the selection criteria, less than -1.0 Z-scores of lumbar spine bone mineral density(BMD) by dual energy X-ray absorptiometry (DEXA). These 30 children were divided into three groups and each were assigned to receive alendronate, calcitriol, and no-medication, respectively for one year. Lumbar spine BMD was followed up every 6 months and the biochemical indexes were measured before and 1 year after the treatment. There were no significant difference among groups with respect to the average age, the initial BMD, and the cumulative steroid doses. Analysis of the treatment efficacy was done by the % change of BMD and by the changes in Z-scores of lumbar spine BMD. Results : Mean age and disease duration of patients at the initial lumbar spine BMD evaluation was $7.4{\pm}1.7$ years and $2.2{\pm}1.2$ years, respectively. Twenty-three of 30 children(76%) had osteopenia, and seven(23%) had osteoporosis. There was no difference in the biochemical values among the groups, before and 1 year after the treatment(P<0.05). Twenty two children(73.3%) with frequent relapsing or steroid dependant NS had more frequent MBD, compared to the 8 children(26.6%) with infrequent relapsing NS. The one year % changes of BMD were 8.56 in alendronate group, 5.79 in calcitriol group, and 1.9 in no-medication group. The changes in Z-score of lumbar spine BMD increased in the alendronate group and the calcitriol group, but not in the no-medication group. One year % changes of BMD were different among groups(P=0.0002). Significant differences were found between the alendronate and the no-medication group, and between the calcitriol and the no-medication group(P<0.05). There was no difference between the alendronate and the calcitriol group. No serious adverse effect was observed in the alendronate group. Conclusion : Children with NS receiving high dose steroids are under the high risk of BMD and should undergo regular BMD evaluation. Z-score of lumbar spine BMD was a useful parameter in diagnosing low bone mass in children. Alendronate weekly oral therapy was effective and relatively safe in increasing the lumbar spine BMD in children with NS having steroid induced MBD.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.309-315
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• 2002

Purpose : To evaluate the result of conservative management on recurrence, survival and prognostic factors of patient with operable breast cancer. Materials and Methods : Fifty three patients, treated for localized breast cancer by lumpectomy or quadrantectomy followed by radiotherapy between January 1985 and December 1996, were retrospectively studied. All patients followed up for at least five years. Their median age was 43 years $(range\;24\~72)$. The tumor stages were as follows : T1 in 30 patients, T2 in 21, Tis in 2. Thirty-eight patients had negative and 15 had positive axillary nodes. The histological types were 42 infiltrating ductal, 2 infiltrating lobular, and 2 intraductal carcinomas with 7 other histologies. The tumor locations were the outer quadrant in 38 breasts, the inner quadrant in 13 and central in 2. Radiation doses of $46\~50\;Gy$ were given to the entire breast areas with additional doses of 14-18 Gy delivered to the tumor bed areas. Results : The overall five and 10 yea actuarial and disease free survivals were $94.3\%\;and\;92.4\%,\;91.2\%\;and\;81\%$, respectively. The overall five year survivals were $100\%$ in stage I and IIa, and $66.7\%$ in stage IIb and IIIa tumors. Seven patients failed either locally or distantly. Incidence of local failure and distant metastasis for the first failure were $7.5\%\;and\;5.7\%$, respectively. Local recurrence appeared within 2 years of treatment at the primary site and after more than 8 years outside of primary lesion, whereas distant metastasis appeared between 2 and 6 years following treatment. The overall recurrences were high at a young age (< or = 35 years), with 5 out of 12 (2 local, 3 distant), and in T2 lesions with 5 out of 21 (1 local, 3 distant, and 1 in both). Distant metastasis was high in the positive axillary lymph node group with 4 out of 15 $(26.6\%)$. A high incidence in the axillary node was noted at a young age with 7 out of 12 $(58.3\%)$ and in T2 lesions with 8 out of 21 $(38.4\%)$. A young age, positive axillary node and large tumor size were all related with poor survival. Conclusion : Based on this study, lumpectomy or quadrantectomy, followed by radiation appears to be an adequate therapeutic method in operable breast cancer. A long term follow-up is necessary because a recurrence of breast can occur long time after treatment. The poor prognostic group, especially young patients with an aggressive biological behavior needs more effective treatment modalities to improve their survival.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.403-409
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• 1995

Purpose : Authors tried to enhance the safety and accuracy of radiosurgery by verifying stereotacitc target point in actual treatment position prior to irradiation. Materials and Methods : Before the actual treatment, several sections of anthropomorphic head phantom were used to create a condition of unknown coordinates of the target point. A film was sandwitched between the phantom sections and punctured by sharp needle tip. The tip of the needle represented the target point. The head phantom was fixed to the stereotactic ring and CT scan was done with CT localizer attached to the ring. After the CT scanning, the stereotactic coordinates of the target point were determined. The head phantom was secured to accelerator's treatment couch and the movement of laser isocenter to the stereotactic coordinates determined by CT scanning was performed using target positioner. Accelerator's anteroposterior and lateral portal films were taken using angiographic localizers. The stereotactic coordinates determined by analysis of portal films were compared with the stereotactic coordinates previously determined by CT scanning. Following the correction of discrepancy the head phantom was irradiated using a stereotactic technique of several arcs. After the irradiation, the film which was sandwitched between the phantom sections was developed and the degree of coincidence between the center of the radiation distribution with the target point represented by the hole in the film was measured. In the treatment of the actual patients, the way of determining the stereotactic coordinates with CT localizers and angiograuhic localizers was the same as the phantom study. After the correction of the discrepancy between two sets of coordinates, we proceeded to the irradiation of the actual patient. Results : In the phantom study, the agreement between the center of the radiation distribution and the localized target point was very good. By measuring optical density profiles of the sandwitched film along axes that intersected the target point, authors could confirm the discrepancy was 0.3 mm. In the treatment of an actual patient, the discrepancy between the stereotactic coordinates with CT localizers and angiographic localizers was 0.6 mm. Conclusion : By verifying stereotactic target point in actual treatment position prior to irradiation, the accuracy and safety of streotactic radiosurgery procedure were established.

• The Korean Journal of Nuclear Medicine
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• v.31 no.3
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• pp.388-394
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• 1997

Temporomandibular (TM) joint Pain results from many etiologic factors. The aim of this study was to evaluate the utility of Bone SPECT in patients with TM joint pain. The subjects were 34 patients with TM joint pain. All patients underwent plain radiography, planar bone scan, and Bone SPECT The intensity of radioisotope uptake at TM joint was graded into three; no increased uptake above the background activity as grade 0, uptake similar to occipital bone as grade I, and uptake similar to maxillary sinus as grade II. Clinical findings and therapeutic methods were reviewed. Twenty-seven patients (80%) out of 34 patients with TM joint pain had increased uptake in bone SPECT. Twenty-one (78%) out of 27 patients had increased uptake in the mandibular condyle and remaining six patients (22%) had uptake in the mandibular and maxillary arch, which proved to be dental problem. Seven patients (21%) out of 34 were grade as 0, four (12%) were grade I, 23 (68%) were grade II. Four patients with grade I had clicking sound and symptoms which were subsided with medication in all cases. Among 23 patients with grade II, 7 patients had clicking sound and 14 patients underwent medication and decompression therapy. With Planar bone scan, 11 cases (32%) had increased uptake in TM joint area. Plain radiography revealed narrowing, distension, erosion and limitation of TM joint in 16 cases (47%). Bone SPECT can be valuable for screening and managing the patients with TM joint pain. Patients with grade II needed intensive treatment such as joint aspiration. However degree of the radioisotope uptake did not well correlated with clinical symptoms.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.478-486
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• 2009

Purpose: 5-iododeoxyuridine analogues have been exclusively developed for the potential antiviral and antitumor therapeutic agents. In this study, we synthesized carbocyclic radioiododeoxyuridineanalogue (ddIVDU) and carbocyclic intermediate as efficient carbocyclic radiopharmaceuticals. Materials and Methods: The synthesis is LAH reduction, hetero Diels-Alder reaction as key reactions including Pd(0)-catalyzed coupling reaction together with organotin. MCA-RH7777 (MCA) and MCA-tk (HSV1-tk positive) cells were treated with various concentration of carbocyclic ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-tk cells were incubated with 1uCi of [$^{125}I$]carbocyclic ddIVDU. Accumulated radioactivity was measured after various incubation times. Results: The synthesis of ddIVDU and precursor for radioiodination were achieved from cyclopentadiene in good overall yield, respectively. The radioiododemetallation for radiolabeling gave more than 80% yield with > 95% radiochemical purity. GCV was more toxic than carbocyclic ddIVDU in MCA-tk cells. Accumulation of [$^{125}I$]carbocyclic ddIVDU was higher in MCA-tk cells than MCA cells. Conclusion: Biological data reveal that ddIVDU is stable in vitro, less toxic than ganciclovir (GCV), and selective in HSV1-tk expressed cells. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5- iodovinyluridine (carbocyclic ddIVDU), is a potential imaging probe for HSV1-tk.