• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.111-111
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• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and G. radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of apoptosis by G. radix are poorly defined. In the present study, it was examined the biochemical mechanisms of apoptosis by water extract of G. radix (WEGR) in human bladder T24 cancer cells. It was found that WEGR could inhibit the cell growth of T24 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by WEGR was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of WEGR induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. WEGR also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that WEGR may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

• Progress in Medical Physics
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• v.14 no.1
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• pp.15-19
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• 2003

High dose rate (HDR) brachytherapy for treating a cervix carcinoma has become popular, because it eliminates many of the problems associated with conventional brachytherapy. In order to improve the clinical effectiveness with HDR brachytherapy, a dose calculation algorithm, optimization procedures, and image registrations need to be verified by comparing the dose distributions from a planning computer and those from a phantom. In this study, the phantom was fabricated in order to verify the absolute doses and the relative dose distributions. The measured doses from the phantom were then compared with the treatment planning system for the dose verification. The phantom needs to be designed such that the dose distributions can be quantitatively evaluated by utilizing the dosimeters with a high spatial resolution. Therefore, the small size of the thermoluminescent dosimeter (TLD) chips with a dimension of <1/8"and film dosimetry with a spatial resolution of <1mm used to measure the radiation dosages in the phantom. The phantom called a pelvic phantom was made from water and the tissue-equivalent acrylic plates. In order to firmly hold the HDR applicators in the water phantom, the applicators were inserted into the grooves of the applicator holder. The dose distributions around the applicators, such as Point A and B, were measured by placing a series of TLD chips (TLD-to-TLD distance: 5mm) in the three TLD holders, and placing three verification films in the orthogonal planes. This study used a Nucletron Plato treatment planning system and a Microselectron Ir-192 source unit. The results showed good agreement between the treatment plan and measurement. The comparisons of the absolute dose showed agreement within $\pm$4.0 % of the dose at point A and B, and the bladder and rectum point. In addition, the relative dose distributions by film dosimetry and those calculated by the planning computer show good agreement. This pelvic phantom could be a useful to verify the dose calculation algorithm and the accuracy of the image localization algorithm in the high dose rate (HDR) planning computer. The dose verification with film dosimetry and TLD as quality assurance (QA) tools are currently being undertaken in the Catholic University, Seoul, Korea.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.51-61
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• 1998

Purpose : Treatment of choice for uterine cervix cancer stage IIB is radiotherapy. We analyzed survivals, Prognostic factors, patterns of failure and complications. Materials and Methods : This is a retrospective analysis of 167 patients with stage IIB carcinoma of uterine cervix treated with curative external pelvic and high dose rate intracavitary radiotherapy at the Department of Therapeutic Radiology, Soonchunhyang University Hospital from August 1985 to August 1994. All the patients followed up from 3 to 141 months(mean 60 months) and age of patients ranged from 31 to 78 years at presentation(mean : 55 years). Results : Overall complete response rate was $84\%$. The response rate for squamous cell carcimoma and adenocarcinoma were $86\%$ and $60\%$, respectively. Overall 5-years survival rate and disease free survival rate was 62 and $59\%$, respectively Mass size and treatment response were significant Prognostic factors for survival Pathologic type and parametrial involvement were marginally significants Prognostic factors. Local failure was 43 cases, distant metastasis was 14 cases and local failure plus distant metastasis was 3 cases, and most of local failures occurred within 24 months, distant metastasis within 12 months after treatment Twenty eight($16.8\%$) patients developed late rectal and urinary complications There were tendency to increasing severity and frequency according to increased fractional dose and total(rectal and bladder) dose. Conclusions : Survival rate was significantly related to tumor size and radiotherapy response. Tumor size should be considered in the clinical s1aging. To increased survival and local control, clinical trials such as decreasing duration of radiotherapy or addition of chemotherapy is needed. To detect early recurrence, regular follow up after RT is important. Because total rectal and bladder dose affected late complications. meticulous vaginal packing is needed to optimize dose of normal tissues and to decrease late complications.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.201-209
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• 1996

Purpose : To assess the efficacy of high dose rate - intracavitary radio-therapy (HDR-ICR) in the radiotherapy of FIGO stage IB squamous cell carcinoma of uterine cervix and to determine the optimum dose combination scheme of external radiotherapy and ICR to achieve acceptable local control without severe complication. Materials and Methods : One hundred and sixty two patients with FIGO stage Ib squamous cell carcinoma of uterine cervix who received definitive radiotherapy between May 1979 and December 1990 were retrospectively analyzed. All the patients received external radiotherapy combined with HDR-ICR. External dose of 40-46 Gy in 4.5-5 weeks was given to whole pelvis(median 45 Gy) and ICR dose of 30-39 Gy in 10-13 times was given to the point A. Midline shielding was done after 20-45 Gy of external radiotherapy(median 40 Gy) Summation of external dose Plus ICR dose to the point A range were 64.20-95.00 Gy. and mean was 83.94 Gy. We analyzed the local control rate, survival rate, and late complication rate. Rusults : Initial complete response rate was $99.4\%$ for all patients. Overall 5-year survival rate was $91.1\%$ and 5-year disease free survival rate was $90.9\%$. Local failure rate was $4.9\%$ and distant failure rate was $4.3\%$. Tumor size was the only significant prognostic factor. When tumor size greater than 3cm, 5-rear survival rate was $92.6\%$ and less than 3cm, that was $79.6\%$. Late complication rate was $23.5\%$ with $18.5\%$ of rectal complication and $4.9\%$ of bladder complication. Mean rectal dose summation of external midline dose plus ICR rectal point dose was lower in the patients without rectal complication(74.88 Gr) than those with rectal complication (78.87 Gy). Complication rate was increased with low rate of improvement of survival rate when summation of external midline dose plus point A or point R dose by ICR was greater than 70-75 Gy. Conclusion : The definitive radiation therapy using high dose rate ICR in FIGO stage IB uterine cervical cancer is effective treatment modality with good local control and survival rate without severe complication.

• Radiation Oncology Journal
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• v.31 no.2
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• pp.104-110
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• 2013

Purpose: Intensity modulated arc therapy (IMAT) is a form of intensity modulated radiation therapy (IMRT) that delivers dose in single or multiple arcs. We compared IMRT plans versus single-arc field (1ARC) and multi-arc fields (3ARC) IMAT plans in high-risk prostate cancer. Materials and Methods: Sixteen patients were studied. Prostate ($PTV_P$), right pelvic ($PTV_{RtLN}$) and left pelvic lymph nodes ($PTV_{LtLN}$), and organs at risk were contoured. $PTV_P$, $PTV_{RtLN}$, and $PTV_{LtLN}$ received 50.40 Gy followed by a boost to $PTV_B$ of 28.80 Gy. Three plans were per patient generated: IMRT, 1ARC, and 3ARC. We recorded the dose to the PTV, the mean dose ($D_{MEAN}$) to the organs at risk, and volume covered by the 50% isodose. Efficiency was evaluated by monitor units (MU) and beam on time (BOT). Conformity index (CI), Paddick gradient index, and homogeneity index (HI) were also calculated. Results: Average Radiation Therapy Oncology Group CI was 1.17, 1.20, and 1.15 for IMRT, 1ARC, and 3ARC, respectively. The plans' HI were within 1% of each other. The $D_{MEAN}$ of bladder was within 2% of each other. The rectum $D_{MEAN}$ in IMRT plans was 10% lower dose than the arc plans (p < 0.0001). The GI of the 3ARC was superior to IMRT by 27.4% (p = 0.006). The average MU was highest in the IMRT plans (1686) versus 1ARC (575) versus 3ARC (1079). The average BOT was 6 minutes for IMRT compared to 1.3 and 2.9 for 1ARC and 3ARC IMAT (p < 0.05). Conclusion: For high-risk prostate cancer, IMAT may offer a favorable dose gradient profile, conformity, MU and BOT compared to IMRT.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.122-132
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• 1998

SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.349-353
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• 1996

The present study examined pharmacokinetic profiles of KBP31705-Cl27 and KBP30603-901, new platinum coordination complexes synthesized as anticancer candidates, in comparison with two well-known platinum-containing anticancer agents, cisplatin and carboplatin in rats. Under sodium pentobarbital anesthesia of male Sprague-Dawley rats, urinary bladder, and femoral artery and vein were catheterized for urine collection, blood sampling and drug injection, respectively Following i.v. administration of cisplatin (2 mg/kg), KBP31705-C127 (2 mg/kg), carboplatin (20 mg/kg) or KBP30603-901 (20 mg/kg), blood samples were collected at 2, 4, 6, 8, 10, 15, 20, 30, 45, 60 and 120 minutes. Urine samples were collected at 1-hr interval for 4 hr. Platinum concentrations in plasma and urine were measured using an inductively coupled plasmamass spectrometer. The plasma concentration-time curves were biphasic for all drugs during the time period studied. Compared with cisplatin, KBP31705-C127 showed similar decay patters in the alpha- and betaphases with slightly lower plasma concentrations. Urinary platinum excretion for cisplatin and KBP31705-C 127 was 56 and 52% of the administered dose in 4 hr, respectively. With regard to carboplatin and KBP 30603-901, a similar decay pattern was also observed in the alpha-phase. The half life of KBP30603-901 in the beta-phase, however, was much longer than that of carboplatin, which was consistent with the urinary excretion results that 46 and 59% of the administered dose were excreted in the urine in 4hr, respectively. The results suggest that platinum coordination complexes are primarily excreted via the renal route and KBP30603-901 can elicit longer duration of action due to slower renal excretion compared to carboplatin.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.241-253
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• 1990

331 patients of stage IIb uterine cervix cancer trated by radiation alone at Kosin Medical Center between June 1980 and Dec. 1985 were analysed to determine parameters of radiotherapy associated to disease states. Survival rate was highest among the reported ($82.8{\%}$ for crude and $82.4{\%}$ for disease free survival). Pelvic control rate in 6 weeks after the end of radiotherapy was $93.6{\%}$ in the patients treated with ICR following total pelvic radiation and $71.6{\%}$ with small field additional external irradiation. 5 year survival rate in those who achieved pelvic control was $98.9{\%}$ and $12.9{\%}$ in those who had pelvic failure and/or metastasis after radiation. The survival rate figured maximal $88.5{\%}$ with dosage of $7500{\~}8500$ cGy to point A with acceptable incidence of complications ($4.9{\%}$) but without increasing survival above it and minimal $74.1{\%}$ with dosage of less than 6500 cGy. The treatment failure was counted $18.7{\%}$ (62 of 331 patients): Local failure $72.6{\%}$ (45 of 62 patients), locoregional failure $3.2{\%}$ (2 of 62 patients) and distant failure $24{\%}$ (15 of 62 patients). Late complications were found in 50 patients ($15.1{\%}$) and $42{\%}$ of them was rectal bleeding and stenosis. The dose of 8500 cGy to point A was found to be critical for complication and $70{\%}$ of complications occurred above it and was more serious one such as fistula. Rectal complications were developed above rectal dose 6500 cGy and bladder complication above bladder dose 7500 cGy. Major cause of death was cachexia due to locoregional failure ($73.7{\%}$ of death), next was due to metastasis to lung, liver and bone, and only 3 patients died of complication of intestinal perforations and obstruction. In conclusion higher external radiation dose for a bulky uterine cervix and barrel shaped uterus was essential for local control.

• The Journal of Korean Society for Radiation Therapy
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• v.25 no.2
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• pp.181-186
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• 2013

Purpose: This study executed therapy plans on prostate cancer (homogeneous density area) and lung cancer (non-homogeneous density area) using radiation treatment planning systems such as $Pinnacle^3$ (version 9.2, Philips Medical Systems, USA) and Eclipse (version 10.0, Varian Medical Systems, USA) in order to quantify the difference between dose calculation according to density in IMRT. Materials and Methods: The subjects were prostate cancer patients (n=5) and lung cancer patients (n=5) who had therapies in our hospital. Identical constraints and optimization process according to the Protocol were administered on the subjects. For the therapy plan of prostate cancer patients, 10 MV and 7Beam were used and 2.5 Gy was prescribed in 28 fx to make 70 Gy in total. For lung cancer patients, 6 MV and 6Beam were used and 2 Gy was prescribed in 33 fx to make 66 Gy in total. Through two therapy planning systems, maximum dose, average dose, and minimum dose of OAR (Organ at Risk) of CTV, PTV and around tumor were investigated. Results: In prostate cancer, both therapy planning systems showed within 2% change of dose of CTV and PTV and normal organs (Bladder, Both femur and Rectum out) near the tumor satisfied the dose constraints. In lung cancer, CTV and PTV showed less than 2% changes in dose and normal organs (Esophagus, Spinal cord and Both lungs) satisfied dose restrictions. However, the minimum dose of Eclipse therapy plan was 1.9% higher in CTV and 3.5% higher in PTV, and in case of both lungs there was 3.0% difference at V5 Gy. Conclusion: Each TPS according to the density satisfied dose limits of our hospital proving the clinical accuracy. It is considered more accurate and precise therapy plan can be made if studies on treatment planning for diverse parts and the application of such TPS are made.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.385-389
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• 2010

Butein(3,4,2',4-tetrahydroxychalcone) has been reported anticancer effects in several cancer type, which is prostate, bladder cancer but breast cancer is not. This study was to investigate the antiproliferative effects by butein(3,4,2',4-tetrahydroxychalcone) in MCF-7 human breast carcinoma cells. We invastigated the effects of dose-dependently cell growth inhibition by butein, which could be proved by WST-1 assay. Also, flow cytometry analysis was butein increase percentage of subG1 phase. As well as, butein induces apoptosis through the expression of caspase-8,-3 and poly(ADP-ribose) polymerase(PARP) activation but not in DMSO treated cells. Taken together, this results suggest that butein induced MCF-7 apoptosis through extrinsic pathway and thus may have potential tumor suppressor in breast cancer.