• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.371-377
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• 2018

The fruits of Panax ginseng were extracted with 80% aqueous MeOH and the concentrates were partitioned into EtOAc, n-BuOH, and $H_2O$ fractions. The repeated $SiO_2$ and octadecyl $SiO_2$ column chromatographies for the EtOAc fraction led to isolation of five ginsenosides. The chemical structures of these compounds were determined as ginsenoside F1 (1), ginsenoside F2 (2), ginsenoside F3 (3), ginsenoside Ia (4), notoginsenoside Fe (5) based on spectroscopic analyses including nuclear magnetic resonance, MS, and infrared. Compounds 2-5 were isolated for the first time from the fruits of P. ginseng in this study. All isolated compounds were evaluated for cytotoxic activities against human cancer cell lines such as HCT-116, SK-OV-3, human cervix adenocarcinoma (HeLa), HepG2, and SK-MEL-5. Among them compounds 2, 4, and 5 showed significant cytotoxicity on cancer cells. Compound 2 exhibited cytotoxicity on SK-MEL-5, HepG2, and HeLa cells with $IC_{50}$ values of 82.8, 86.8, and $78.3{\mu}M$, respectively. Compound 4 showed cytotoxicity on HCT-116, SK-MEL-5, SK-OV-3, HepG2, and HeLa cells with $IC_{50}$ values of 24.5, 25.4, 26.3, 22.0, and $24.9{\mu}M$, respectively. Compound 5 did on SK-MEL-5 cell with $IC_{50}$ value of $81.7{\mu}M$. The cytotoxicity of ginsenoside 2, 4, and 5 isolated from the fruits of Panax ginseng showed strong inhibition effect against on cancer cells, all of which have a glucopyranosyl moiety on C-3.

• Journal of Life Science
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• v.32 no.4
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• pp.271-278
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• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

• Journal of Radiation Protection and Research
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• v.32 no.4
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• pp.140-156
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• 2007

This research was performed to investigate the morphological changes of folliculus ovary according to the radiation dose. The whole body radiation of 200 cGy, 400 cGy, and 600 cGy was given to the each groups of 5 months-aged female mouse. Various staining methods used in this research are: Hematosylin-Eosin method, and immunohistochemistrical methods using BrdU, TUNEL, p53, p21, PCNA and inhibin. The minute structural changes of folliculus ovary were observed through an electron microscope with high magnification. The morphological changes of growing folliculus ovary became distinct as the dose of X-rays increased. Especially, the nuclei of granular cells showed manifest condensation and the changes of the transparent zone were distinct. As a result of histochemical reaction according to Masson's trichrome method and reticular fiber method, the changed granular cells, the deformed basilar membrane of folliculus ovary and the abnormal arrangement of the reticular fiber were observed. In the reaction of BrdU, the granular cells of normal folliculus ovary with positive reaction rapidly decreased according to the increase of the dose of X-rays. In TUNEL study, granular cells showing positive reaction in retarded folliculus ovary were expanded to growing folliculus ovary and primordial folliculus ovary according to the increase of the dose of X-rays. In case of 600 cGy of X-rays, oocyte underwent apoptosis. In p53 immunohistochemistry, p53 manifested to be stronger as the dose of X-rays increased. p53 reactivity was manifested distinctively in all cells comprising folliculus ovary following irradiation of 600 cGy. p21 was manifested in granular cells of folliculus ovary and showed very positive reaction around follicular antrum according to the increase of the dose of X-rays. In PCNA, positive reaction was manifested in growing folliculus ovary, mature folliculus ovary and primordial folliculus ovary, but the extent of the reaction decreased as the dose of the X-rays decreased. The finding that the reaction of granular cells around folliculus ovary was stronger than that near follicular membrane indicates that what was damaged first by X-ray was the cells near folliculus ovary and follicular antrum. The reactivity of $inhibin-{\alpha}$ showed difference according to the growing stage of folliculus ovary: $inhibin-{\alpha}$ showed the most strong reaction in mature folliculus ovary with follicular antrum. There was strong reaction in granular cells around follicular membrane but $inhibin-{\alpha}$ did not occur at all in theca cells comprising follicular membrane. $Inhibin-{\alpha}$ in ovary tissue exposed to 400 cGy of X-rays was manifested more strongly than in ovary tissue exposed to 600 cGy of X-rays, which was related to the phenomenon that granular cells of mature folliculus ovary underwent necrosis or apoptosis increasingly due to X-rays. In an electron microscope with high magnification, nuclei and protoplasm of granular cells in growing folliculus ovary abruptly underwent minute structural changes according to the increase of dose of X-rays. Cell residue, by-product of cell decease, neutrophil and macrophage around follicular antrum were observed. The minute structural changes in granular cells showed typical characteristics of apoptosis: the increase of electronic density due to nuclear condensation, fragmentation of nuclei and atrophy of protoplasm. Necrosis of cells was identified but it was not so remarkable. Macrophage with apoptotic bodies was scattered. Proportional to the radiation dose, we found that the generation of heterogeneous substance of normal ovary texture's follicular fluid, the emergence of dyeing characteristic in the basilar membrane of folicle, the generation of apoptosis, and the transformation of macrophages, etc. From this results, we can infer the possible radiation hazard on the ovary of cervix cancer patient with radiation therapy.

• Radiation Oncology Journal
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• v.23 no.4
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• pp.223-229
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• 2005

Purpose: In this work we designed and made MPBP(Multi Purpose Brachytherapy Phantom). The MPBP enables one to reproduce the same patient set-up in MPBP as the treatment of the patient and we tried to get an exact analysis of rectal doses in the phantom without need of in-vivo dosimetry. Materials and Methods: Dose measurements were tried at a point of rectum 1, the reference point of rectum, with a diode detector for 4 patients treated with tandem and ovoid for a brachytherapy of a cervix cancer. Total 20 times of rectal dose measurements were made with 5 times a patient. The set-up variation of the diode detector was analyzed. The same patient set-ups were reproduced in self-made MPBP and then rectal doses were measured with TLD. Results: The measurement results of the diode detector showed that the set-up variation of the diode detector was the maximum $11.25{\pm}0.95mm$ in the y-direction for Patient 1 and the maximum $9.90{\pm}4.50mm,\;20.85{\pm}4.50mm,\;and\;19.15{\pm}3.33mm$ in the z-direction for Patient 2, 3, and 4, respectively. Un analyzing the degree of variation in 3 directions the more variation was showed in the z-direction than x- and y-direction except Patient 1. The results of TLD measurements in MPBP showed the relative maximum error of 8.6% and 7.7% at a point of rectum 1 for Patient 1 and 4, respectively and 1.7% and 1.2% for Patient 2 and 3, respectively. The doses measured at R1 and R2 were higher than those calculated except R point of Patient 2. this can be thought to related to the algorithm of dose calculation, whcih corrects for air and water but is guessed not to consider the correction for the scattered rays, but by considering the self-error (${\pm}5%$) TLD has the relative error of values measured and calculated was analyzed to be in a good agreement within 15%. Conclusion: The reproducibility of dose measurements under the same condition as the treatment could be achieved owing to the self-made MPMP and the dose at the point of interest could be analyzed accurately. If a treatment is peformed after achieving dose optimization using the data obtained in the phantom, dose will be able to be minimized to important organs.

• The Journal of Korean Society for Radiation Therapy
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• v.16 no.2
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• pp.9-17
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• 2004

Purpose : Although Improve of CT, MRI Radio-diagnosis and Radiation Therapy Planing, but we still use ICRU38 Planning system(2D film-based) broadly. 3-Dimensional ICR plan(CT image based) is not only offer tumor and normal tissue dose but also support DVH information. On this study, we plan irradiation-goal dose on CTV(CTV plan) and irradiation-goal dose on ICRU 38 point(ICRU38 plan) by use CT image. And compare with tumor-dose, rectal-dose, bladder-dose on both planning, and analysis DVH Method and Material : Sample 11 patients who treated by Ir-192 HDR. After 40Gy external radiation therapy, ICR plan established. All the patients carry out CT-image scanned by CT-simulator. And we use PLATO(Nucletron) v.14.2 planing system. We draw CTV, rectum, bladder on the CT image. And establish plan irradiation-$100\%$ dose on CTV(CTV plan) and irradiation-$100\%$ dose on A-point(ICRU38 plan) Result : CTV volume($average{\pm}SD$) is $21.8{\pm}26.6cm^3$, rectum volume($average{\pm}SD$) is $60.9{\pm}25.0cm^3$, bladder volume($average{\pm}SD$) is $116.1{\pm}40.1cm^3$ sampled 11 patients. The volume including $100\%$ dose is $126.7{\pm}18.9cm^3$ on ICRU plan and $98.2{\pm}74.5cm^3$ on CTV plan. On ICRU planning, the other one's $22.0cm^3$ CTV volume who residual tumor size excess 4cm is not including $100\%$ isodose. 8 patient's $12.9{\pm}5.9cm^3$ tumor volume who residual tumor size belows 4cm irradiated $100\%$ dose. Bladder dose(recommended by ICRU 38) is $90.1{\pm}21.3\%$ on ICRU plan, $68.7{\pm}26.6\%$ on CTV plan, and rectal dose is $86.4{\pm}18.3\%,\;76.9{\pm}15.6\%$. Bladder and Rectum maximum dose is $137.2{\pm}50.1\%,\;101.1{\pm}41.8\%$ on ICRU plan, $107.6{\pm}47.9\%,\;86.9{\pm}30.8\%$ on CTV plan. Therefore CTV plan more less normal issue-irradiated dose than ICRU plan. But one patient case who residual tumor size excess 4cm, Normal tissue dose more higher than critical dose remarkably on CTV plan. $80\%$over-Irradiated rectal dose(V80rec) is $1.8{\pm}2.4cm^3$ on ICRU plan, $0.7{\pm}1.0cm^3$ on CTV plan. $80\%$over-Irradiated bladder dose(V80bla) is $12.2{\pm}8.9cm^3$ on ICRU plan, $3.5{\pm}4.1cm^3$ on CTV plan. Likewise, CTV plan more less irradiated normal tissue than ICRU38 plan. Conclusion : Although, prove effect and stability about previous ICRU plan, if we use CTV plan by CT image, we will reduce normal tissue dose and irradiated goal-dose at residual tumor on small residual tumor case. But bigger residual tumor case, we need more research about effective 3D-planning.

• The Journal of Korean Society for Radiation Therapy
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• v.17 no.1
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• pp.1-8
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• 2005

Purpose : An effect of a packing to uterine treatment of a cervical cancer using a dose-volume histogram for a point dose and a volume dose of the bladder and the rectum was analyzed by establishing a three-dimensional treatment plan using a CT image. Materials and methods : Reference points of the bladder and the rectum were marked, respectively at a treatment plan device (plato brachytherapy V14.2.4) by photographing CT(marconi, USA) when the packing was used and removed under the same condition and a treatment plan was performed to Apoint depending on ICRU38. However, in case of the rectum, a maximum point was looked up and compared with the above point because the point presented from the ICRU is not proper as a representative value of a rectum point dose. Further, the volume dose depending on volume of $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder was measured. The measured values were used to analyze the effect of the packing through a Wilcoxon Signed Rank Test (a SAS statistical analysis process program). Result : The reference points at the bladder and rectum doses when the packing was removed were $116.94\;35.42\%$ and $117.59\;21.08\%$, respectively. The points when the packing was used were $107.08\;38.12\%$ and $95.19\;21.32\%$, respectively. After the packing was used, the reference points at the bladder and the rectum were decreased by $9.86\%$ and $22.4\%$, respectively. When the packing was removed, the maximum points at the bladder and the rectum were $164.51\;50.89\%,\;128.81\;33.05\%$, respectively. When the packing was used, the maximum points at the bladder and the rectum were $142.31\;44.79,\;110.08\;37.03\%$, respectively. After the packing was used, the maximum points at the bladder and the rectum were decreased by $22.2\%$ and $18.73\%$, respectively. When the packing was removed, the bladder volume at $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder were $48.62{\pm}18.09\%,\;16.12{\pm}11.15\%,\;and\;7.51{\pm}6.63\%$, respectively and its rectum volume were $23.41{\pm}14.44\%,\;6.27{\pm}4.28\%,\;2.79{\pm}2.27\%$, respectively. When the packing was used, the bladder volume at $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder were $40.33{\pm}16.72,\;11.63{\pm}8.72,\;and\;4.87{\pm}4.75\%$, respectively and its rectum volume were $18.96{\pm}8.37\%,\;4.75{\pm}2.58\%,\;and\;1.58{\pm}1.06\%$, respectively. After the packing was used, the bladder volume at $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder were decreased by $8.29\%,\;4.49\%,\;and\;2.64\%$, respectively and its bladder volume were decreased by $4.45\%,\;1.52\%,\;and\;1.21\%$, respectively. Conclusion : Values at Reference point doses of the bladder and the rectum recommended from the ICRU 38 were 0.0781 and 0.0781, respectively and values of their maximum point doses were 0.0156 and 0.0156, respectively, as a result of which an effect of the packing using at the uterine intracavitary treatment of an uterine cervical cancer through the three-dimensional treatment plan used CT were measured. That is, the values at reference point doses and the values at maximum point doses show similar difference. However, P value was 0.15 at over $50\%,\;80\%,\;and\;100\%$ volume doses and the value shows no similar difference. In other words, the effect of the packing looks like having a difference at the point dose, but actually shows no difference at the volume dose. The reason is that the volume of the bladder and the rectum are wide but the volume of the packing is only a portion. Therefore, the effect of decreasing the point dose was not great. Further, the farer the distance is, the more weak the intensity of radiation is because the intensity of radiation is proportional to inverse square of a distance. Therefore, the effort to minimize an obstacle of the bladder and the rectum by using the packing should be made.