• Radiation Oncology Journal
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• v.15 no.1
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• pp.11-18
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• 1997

Purpose : To evaluate the efficacy of combined treatment of surgery and chemoradiotherapy for supratentorial primitive neuroectodermal tumors (SPNET) and obtain the Prognostic factors and complications Materials and Methods .The a9e of 18 patients ranged from 1 to 27 years (median=5 years). There were 12 males and 6 females The extents of surgery were gross total (n:9), subtotal (n:8), biopsy only (n: 1). Craniospinal radiotherapy was delivered to all the patients except 2 patients who were treated only with the whole brain and primary lesion. Radiation dose were 3120-5800cGy (median=5460) to primary mass, 1500-4200cGy (median=3600cGy) to the whole brain and 1320-3600cGy (median= 2400 cGy) to the spinal axis. Chemotherapy was done in 13 patients. Median follow-up period was 45 months ranged from 1 to 89 months. Results : Patterns of failure were as follows; local recurrence (1), multiple intracranial recurrence (2), spinal seeding (3), craniospinal seeding (2) and multiple bone metastasis (1). Two of two patients who did not received craniospinal radiotherapy failed at spinal area. All the relapsed cases died at 1 to 13 months after diagnosis of progression. The 2- and 5-rear overall survival rates were $61\%\;and\;49\%$, respectively The a9e, sex, tumor location did not influence the survival but aggressive resection with combined chemotherapy showed better outcome. Among 9 survivors, complications were detected as radiation necrosis (n=1), hypopituitarism (n=2), cognitive defect(n=1), memory deficit (n=1), growth retardation (n=1). Conclusion : To improve the results of treatment of SPNET, maximal surgical resection followed by radiation therapy and chemotherapy is necessary. The extended radiation field including craniospinal axis may reduce the recurrence in spinal axis.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.289-294
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• 2008

Purpose: To improve the quality of the statistical analysis of papers published in the Journal of the Korean Society for Therapeutic Radiology and Oncology (JKOSTRO) by evaluating commonly encountered errors. Materials and Methods: Papers published in the JKOSTRO from January 2006 to December 2007 were reviewed for methodological and statistical validity using a modified version of Ahn's checklist. A statistician reviewed individual papers and evaluated the list items in the checklist for each paper. To avoid the potential assessment error by the statistician who lacks expertise in the field of radiation oncology; the editorial board of the JKOSTRO reviewed each checklist for individual articles. A frequency analysis of the list items was performed using SAS (version 9.0, SAS Institute, NC, USA) software. Results: A total of 73 papers including 5 case reports and 68 original articles were reviewed. Inferential statistics was used in 46 papers. The most commonly adopted statistical methodology was a survival analysis (58.7%). Only 19% of papers were free of statistical errors. Errors of omission were encountered in 34 (50.0%) papers. Errors of commission were encountered in 35 (51.5%) papers. Twenty-one papers (30.9%) had both errors of omission and commission. Conclusion: A variety of statistical errors were encountered in papers published in the JKOSTRO. The current study suggests that a more thorough review of the statistical analysis is needed for manuscripts submitted in the JKOSTRO.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.80-80
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• 2003

${\beta}$-lapachone(${\beta}$-Lap), a natural o-naphthoquinone, presents in the bark of the Lapacho tree. ${\beta}$-Lap is cytotoxic against a variety of human cancer cells and it potentiates the anti-tumor effect of Taxol. In addition, ${\beta}$-Lap has been reported to radiosensitize cancer cells by inhibiting the repair of radiation-induced DNA damage.In the present study, we investigated the cytotoxicity of ${\beta}$-Lap against RKO human colorectal cancer cells as well as the combined effect of ${\beta}$-LaP and ionizing radiation. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h killed almost 90％ of the clonogenic cells. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h or longer also caused massive apoptosis. Unlike other cytotoxic agents, ${\beta}$-Lap did not increase the expression of p53 and p21 and it suppressed the NFkB expression. The expression of Caspase 9 and 3 was minimally altered by ${\beta}$-Lap. Radiation and ${\beta}$-Lap acted synergistically in inducing clonogenic cell death and apoptosis in RKO cells when ${\beta}$-Lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 ${\mu}$M of ${\beta}$-Lap starting 5 h after irradiation was as effective as that starting immediately after irradiation. The mechanisms of ${\beta}$-Lap-induced cell killing is controversial but a recent hypothesis is that ${\beta}$-Lap is activated by NAD(P)H: quinone-onidoreductase (NQO1) in the cells followed by an elevation of cytosolic Ca$\^$2+/ level and activation of proteases leading to apoptosis. It has been reported that NQO1 level in cells is markedly up-regulated for longer than 10 h after irradiation. Indeed, using immunological staining of NQO1, we observed a significant elevation of NQO1 expression in RKO cells 5h after 2-4 Gy irradiation. Such a prolonged elevation of NQO1 level after irradiation may be the reasons why the ${\beta}$-Lap treatment applied S h after irradiation was as effective as that applied immediately after irradiation in killing the cells. In view of the fact that the repair of radiation-induced damage is usually completed within 1-2 h after irradiation, it is highly likely that the ${\beta}$-Lap treahment applied 5 h after irradiation could not inhibit the repair of radiation-induced damage. For in vivo study, RKO cells were injected S.C. into the hind-leg of Nu/Nu mice, and allowed to grow to 130 mm3 tumor. The mice were i.p. injected with ${\beta}$-lapachone or saline 2 h after irradiation of tumors with 10 Gy of X-rays. The radiation induced growth delay was increased by 2.4 $\mu\textrm{g}$/g of ${\beta}$-lapachone. Taken together, we may conclude that the synergistic interaction of radiation and ${\beta}$-Lap in killing cancer cells is not due to radiosensitization by ${\beta}$-Lap but to an enhancement of ${\beta}$-Lap cytotoxicity by radiation through an upregulation of NQO1. The fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferentially kill tumor cells using ${\beta}$-Lap in combination with radiotherapy.

• Journal of Radiation Protection and Research
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• v.18 no.2
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• pp.1-16
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• 1993

As guides to decision-making in the management of the victims in case of acute whole body or partial body radiation exposure, we studied the relationship between radiation dose and the frequency of chromosomal aberrations observed in peripheral lymphocytes that were irradiated in vitro with $^{60}Co\;{\gamma}-rays$ at doses ranging from 2Gy to 12Gy. The yields of cells with unstable chromosomal aberrations (dicentric chromosomes, ring chromosomes, and acentric fragment pairs) were 32% at 2Gy, 47% at 4Gy, 80% at 6Gy, 94% at 8Gy, and 100% at 10Gy and over. Ydr, which reflect average dose to the whole body in case of acute whole body exposure, were 1.373 at 2Gy, 0.669 at 4Gy, 1.734 at 6Gy, 2.773 at 8Gy, 3.746 at 10Gy and 5.454 at 12Gy. The relationship between radiation dose (D) and the frequency of dicentric plus ring chromosomes per cell(Ydr) could be expressed as $Ydr=9.322{\times}10^{-2}/Gy {\times}D+2.975{\times}10^{-2}/Gy^2{\times}D^2$. Qdr, which are used in estimating dose of partial body exposure and dose of past exposure, were 1.166 at 2Gy, 1.436 at 4Gy, 2.173 at 6Gy, 2.945 at 8Gy, 3.746 at 10Gy and 5.454 at 12Gy. To see how confidently this dosimetry system may be used, we obtained Qdr values from those who received one fraction of homogenous partial body irradiation of 1.BGy, 2.5Gy, and 7.OGy therapeutically; in vivo Qdr values were 1.109, 1.222 and 2.222 respectively. The estimated doses calculated from these in vivo Qdr values using the equation $Qdr=Ydr/(1- e^{-Ydr})$ were 1.52Gy, 2.48Gy, and 6.54Gy respectively, which were very close to the doses actually given.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.271-276
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• 1991

A series of 510 patients with carcinoma of the uterine cervix given the curative radiation therapy from March 1979 through December 1986 was evaluated to determine the value of intravenous pyelography (IVP), cystoscopy, sigmoidoscopy, and abdomino-pelvic CT as staging work-up prior to treatment. On IVP and cystoscopy, $10.7\%$(49/456) and $5.3\%$(24/452) showed abnormality, respectively, but only $0.7\%$(3/413) did on sigmoidoscopy. As a result of these work-ups prerequisite to FIGO staging, twenty six ($5.1\%$) out of 510 patients were upstaged from the stage determined by the findings of physical examination alone. The proportions of upstaging in each stage were as follows; none in stage IB (35), IIA (89) and IIIA (8), $7.9\%$(20/252) in stage IIB (14 patients to FIGO stage IIIB, 6 patients to FIGO stage IVA), and $4.8\%$(6/126) in stage IIIB (all to FIGO stage IVA). Positive findings of staging work-ups were found only in patients with advanced stages of stage IIB or over determined by physical examination alone but not in those with earlier stages. CT was performed in 337 patients. CT detected pelvic lymph node (LN) enlargement in $25.2\%$ (85/337) and paraaortic LN enlargement in $7.4\%$(25/337). Pelvic LN positivity was well correlated with increasing stage but paraaortic LN positivity was not. In the evaluation of parametrial involvement, CT findings were in accordance with those of physical examination only in $65.6\%$ (442/674). When compared with endoscopic studeies, CT had much lower positive predictive value than negative predicitive value in the evaluation of adjacent organ invasion. The staging work-ups should be individualized by the disease extent of each patient, and then the efficiency of work-uus may be increased without compromising the appropriate FIGO staging and treatment.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.249-252
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• 1991

A Retrospective study to analyze the failure pattern in locally advanced stomach cancer, treated with radical surgery and post-op chemotherapy was perfomed. Among 107 patients who underwent radical gastrectomy in Asan Medical Center between June 1989 and August 1990. there were 20 stage II(T2NO, T2N1) and 87 stage III(T3N1, T3N2) and 91 patients were eligible for study. 57 patients treated with 6 cycles of postop adjuvant chemotherapy. Among 57 patients treated with postop adjuvant chemotherapy, local failure occurred in $21\%$ and distant failure in $12\%$. Among 34 patients who were not treated with postop chemotherapy, local failure occurred in $24\%$ and distant failure in $26\%$. Among 29 failures including 13 locoregional, 9 distant metastasis and 7 locoregional and distant metastasis, 11 cases recurred in the anastomotic site, 3 in the gastric bed,7 in the regional lymph nodes and peritoneal seeding occurred in 6 cases. The true incidences of gastric bed, nodal and peritoneal failures may be higher in the longer follow-up or reoperative or autopsy series. Our data sugest that postop chemocherapy is beneficial by reducing distant failure rate. Our data suggest that postop chemocherapy is beneficial by reducing distant failure rate. Postop adjuvant locoregional radiotherapy in addition to the systemic adjuvant therapy may reduce the local failure rate and potentially benefit in at least $20\%$ of patients who developed the local failure only.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.224-229
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• 2001

Purpose : The aim of this study is to analyze the treatment failure patterns and the risk factors for locoregional or distant failure of uterine cervical carcinoma treated with radiation therapy. Materials and methods . A retrospective analysis was undertaken of 154 patients treated with curative radiation therapy in Gyeongsang National University Hospital from April 1989 through December 1997. According to FIGO classification, 12 patients were stage IB, 24 were IIA, 98 were IIB, 1 were IIIA, 17 were IIIB, 2 were IVA. Results : Overall treatment failure rate was $42.1\%$ (65/154), and that of complete responder was $31.5\%$ (41/130). Among 65 failures, 25 failed locoregionally, another 25 failed distantly, and 15 failed locoregionally and distantly. Multivariate analysis confirmed tumor size (>4 cm) as risk factor for locoregional failure, and tumor size (>4 cm), pelvic lymph node involvement as risk factors for distant failure. Conclusion : On the basis of results of our study and recent published data of prospective randomized study for locally advanced uterine cervical carcinoma, we concluded that uterine cervical carcinoma with size more than 4 cm or pelvic lymph node involvement should be treated with concurrent chemoradiation.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.252-258
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• 2001

Purpose : The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after $\gamma-ray$ irradiation in human H&N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and method : Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. Results : Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index. Apoptotic fractions at 2 Gy were $46\%,\;48\%,\;46\%,\;24\%,\;and\;19\%$ and at 6 Gy were $20\%,\;33\%,\;35\%,\;17\%,\;and\;20\%$ for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy, but there was not such correlation at 6 Gy. Conclusion : All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important mode of cell death than apoptotic death in all cell lines used in this study. But there was correlation between apoptotic fraction and radiation sensitivity at 2 Gy.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.265-270
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• 2004

Purpose: To evaluate the effectiveness of postoperative radiation therapy in cervical cancer patients and define the prognostic factors to affect survival rates. Materials and Methods: Eighty one patients with cervical cancer who were treated with postoperative radiation therapy following surgery at our institution between May 1992 and April 2000 were retrospectivelv analyzed. Forty two patients had stage IB disease, 17 had stage IIA disease, and remaining 22 had stage IIB disease, respectively. Histological examination revealed 76 squamous cell carcinoma and 5 adenocarclnoma. Sixty one patients were noted to have stromal invasion greater than 8 mm and 20 patients were noted to have stromal invasion 7 mm or less. Sixteen patients had parametrial invasion and 65 patients did not. Positive vaginal resection margin was documented in only eight patients and positive lymphovascular invasion was in twelve patients. All of the patients were treated with external beam radiation therapy alone. Majority of the patients were treated with 4 field brick technique to encompass whole pelvis. Total of 5,500 cGy was delivered to the primary surgical tumor bed. Minimum follow up period was four years. Results: Actuarial disease free survival rates for entire group of the patients were 95% and 89% at 2 and 5 years, respectively Five year disease free survival rates for patients with stage IB, IIA, and IIB disease were 97%, 87% and 70%, respectivelv. Local recurrences were documented in 5 patients. Cumulative local failure rate at 3 years was 6% Five year disease free survival rates for patients with stromal invasion greater than 8 mm and 7 mm or less were 88% and 92%, respectively (p>0.05). Five year disease free survival rate for patients with parametrial invasion was significantly lower than those with no invasion (72% vs 92%, p<0.05). Also there was significantly lower survival in patients with positive vaginal resection margin, compared with patients with negative resection margin (64% vs 94%, p<0.05). However, lymphovascular invasion was not a statistically significant prognostic factor Parametrial invasion and positive surgical resection margins were noted to be significant prognostic factors. Conclusions: Postoperative radiation therapy appears to be beneficial in controlling local disease in cervical cancer patients with high pathologic risk factors. Parametrial invasion and positive resection margins were noted to be significant prognostic factors to affect survival and more effective treatment should be investigated in these patients.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.205-214
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• 1995

Purpose : To investigate the effect of Ginkgo biloba extract (GBE) on hypoxic cell fraction and metabolic status in fibrosarcoma (FSa II) of C3H mouse. Materials and Methods : Fibrosarcoma (FSa II) 6 mm in diameter, growing in the right hindleg muscle of C3H mouse was used for estimation of hypoxic cell fraction using comparison of $TCD_{50}$. Radiation was given one hour after administration of GBE (100 mg/kg. i.p.) with or without priming dose of GBE (100 mg/kg, i.p.) given 24 hours earlier. Radiation was also given under air breathing condition or clamp hypoxia without GBE as controls. $^{31}p$ NMR spectroscopy was performed before and one hour after administration of GBE with or without priming dose of GBE. Results : $TCD_{50/120's}$ were 81.7 (77.7-86.0) Gy when irradiated under clamped hypoxia 69.6 (66.8-72.5) Gy under air breathing condition. 67.5 (64.1-71.1) Gy with a single dose of GBE (100 mg/kg) given one hour before irradiation, and 62.2 (59.1-65.5) Gy with two doses of GBE given at 25 hours and one hour before irradiation. The hypoxic cell fractions, estimated from $TCD_{50/120's}$, were $10.6{\%}$ under air breathing condition, $7.2{\%}$ after a single dose of GBE, and $2.7{\%}$ after two doses of GBE. The results of $^{31}P$ NMR spectroscopy were as follow. PCr/Pi ratio was $0.27{\pm}0.04$ and $0.40{\pm}0.04$ before and one hour after a single dose of GBE (p<0.05), respectively, without priming dose and $0.30{\pm}0.02$ and $0.71{\pm}0.04$, respectively, with priming dose (p<0.01). These findings indicate that the metabolic status is slightly improved after a single dose and markedly after repeated administrations. Conclusion : GBE decreases the hypoxic cell fraction and imprvoes the meta bolic status of tumor, probably by increasing the blood flow and delivery of oxygen and nutrients, resulting in increased radiosensitivity of tumor.