• 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.14 no.1
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• pp.41-52
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• 1996

Purpose : This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum, external radiation dose to the whole pelvis, ICR reference volume, TDF BED and the incidence of late rectal complications, retrospectively. Materials and Methods : From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department of Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachytherapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r, R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. Results : Twenty seven($30.7\%$) of the 88 patients developed late rectal complications:12 patients($13.6\%$) for grade 1, 12 patients($13.6\%$) for grade 2 and 3 patients($3.4\%$) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complication. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was Higher, $4093.3\pm453.1$ cGy, than that for the patients without complication, $3873.8\pm415.6$ (0.05$7163.0\pm838.5$ cGy, than that for the Patients without rectal complication, $0772.7\pm884.0$ (p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the iCR rectal doses(r, dr), ICR reference volume, TDF and BED. Conclusion : This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R) dose to the whole pelvis and the incidence of grade 2, 3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HOR ICR. Thus these rectal reference points doses and whole pelvis dose appear to be useful Prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.270-278
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• 2018

This study was conducted to compare the anesthetic effects of 2,2,2-tribromoethanol (TBE, $Avertin^{(R)}$) in ICR mice obtained from three different sources. TBE (2.5%) was intraperitoneally injected at three doses: high-dose group (500 mg/kg), intermediate-dose group (250 mg/kg), and low-dose group (125 mg/kg). Anesthesia time, recovery time, end-tidal peak $CO_2$ ($ETCO_2$), mean arterial blood pressure, heart rate, oxygen saturation ($SpO_2$), body temperature, pH, $PCO_2$, and $PO_2$ of the arterial blood were measured. Stable anesthesia was induced by all doses of TBE and the anesthesia time was maintained exhibited dose dependency. No significant differences in anesthetic duration were found among the three different strains. However, the anesthesia time was longer in female than in male mice, and the duration of anesthesia was significantly longer in female than in male mice in the high-dose group. The recovery time was significantly longer for female than male mice in the intermediate- and high-dose groups. In the ICR strains tested, there were no significant differences in the mean arterial blood pressure, $SPO_2$, arterial blood $PCO_2$, and $PO_2$, which decreased after TBE anesthesia, or in heart rate and $ETCO_2$, which increased after TBE anesthesia. In addition, body temperature, blood biochemical markers, and histopathological changes of the liver, kidney, and lung were not significantly changed by TBE anesthesia. These results suggested that ICR mice from different sources exhibited similar overall responses to a single exposure to TBE anesthesia. In conclusion, TBE is a useful drug that can induce similar anesthetic effects in three different strains of ICR mice.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.387-392
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• 1994

Purpose : This study was done to confirm the reference point variation according to variation in applicator configuration in each fractioation of HDR ICR. Materials and Methods : We analyzed the treatment planning of HDRICR for 33 uterine cervical cancer patients treated in department of therapeutic radiology from January 1992 to February 1992. Analysis was done with respect to three view points-Interfractionation A point variation, interfractionation bladder and rectum dose ratio variation, interfractionation treatment volume variation. Interfractionation A point variation was defined as difference between maximum and minimum distance from fixed rectal point to A point in each patient. Interfractionation bladder and rectum dose ratio variation was defined as difference between maximum and minimum dose ratio of bladder or rectum to A point dose in each patient, Interfractionation treatment volume variation was defined as difference between miximum and minimum treatment volume which absorbed over the described dose-that is, 350 cGy or 400 cGy-in each patient. Results The mean of distance from rectum to A point was 4.44cm, and the mean of interfractionation distance variation was 1.14 cm in right side,1.09 cm in left side. The mean of bladder and rectum dose ratio was $63.8\%$ and $63.1\%$ and the mean of interfractionation variation was $14.9\%$ and $15.8\%$ respectively. With fixed planning administration of same planning to all fractionations as in first fractionation planning-mean of bladder and rectum dose ratio was $64.9\%$ and $72.3\%$.and the mean of interfraction variation was $28.1\%$ and $48.1\%$ reapectively. The mean of treatment volume was $84.15cm^3$ and the interfractionation variation was $21.47cm^2$. Conclusion : From these data, it was confirmed that there should be adapted planning for every fractionation ,and that confirmation device installed in ICR room would reduce the interfractionation variation due to more stable applicator configuration.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.231-239
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• 1990

From May 1979 through December 1981 a total of 524 patients with carcinoma of the uterine cervix were treated by radiation therapy with curative intent. Among the 524 patients, 350 were treated with a high-dose-rate (HDR), remote-controlled, afterloading intracavitary irradiation (ICR) system using a cobalt source (Ralstron), and 168 patients received a low-dose-rate (LDR) ICR using a radium source. External beam irradiation with a total dose of 40-50 Gy to the whole pelvis followed by intracavitary irradiation with a total dose of 30-39 Gy in 10-13 fractions to point A was the treatment protocol. ICR was given three times a week with a dose of 3 Gy per fraction. Five-year actuarial survival rates in the HDR-ICR group were $77.6{\%}$ in stage IB (N=20), $68.2{\%}$ in stage II (N=182), and $50.9{\%}$ in stage III (N=148). In LDR-ICR group, 5-year survival rates were $87.5{\%}$ in stage IB (N=22), $66.3{\%}$ in stage II (N=91), and $55.4{\%}$ in stage III (N=52). Survival rates showed a statistically significant difference by stage, but there was no significant difference between the two ICR groups. Late bowel complications after radiotherapy were noted in $3.7{\%}$ of the HDR-ICR group and $8.4{\%}$ of the LDR-ICR group. There was no severe complication requiring surgical management. The incidence of bladder complications was $1.4{\%}$ in the HDR-ICR group and $2.4{\%}$ in the LDR-ICR group. The application of HDR-ICR was technically simple and easily performed on an outpatient basis without anesthesia, and the patients tolerated it very well. Radiation exposure to personnel was virtually nil in contrast to that of LDR-ICR. Within a given period of time, more patients can be treated with HDR-ICR because of the short treatment time. Therefore, the HDR-ICR system is highly recommended for a cancer center, particularly one with a large number of patients to be treated. In order to achieve an improved outcome, however, the optimum dose-fractionation schedule of HDR-ICR and optimum combination of intracavitary irradiation with external beam irradiation should be determined through an extensive protocol.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.276-282
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• 2003

Purpose: Although high-dose-rate intracavitary radiotherapy (HDR ICR) has been used in the treatment of cervical cancer, the potential for increased risk of late complication, most commonly in the rectum, is a major concern. We have previously reported on 136 patients treated with HDR brachytherapy between 1995 and 1999. The purpose of this study is to upgrade the previous data and confirm the correlation between late rectal complication and rectal dose in cervix cancer patients treated with HDR ICR. Materials and Methods: A retrospective analysis was peformed for 222 patients with cevix cancer who were treated for curative intent with external beam radiotherapy (EBRT) and HDR ICR from July 1995 to December 2001. The median dose of EBRT was 50.4 (30.6$\~$56.4) Gy with a daily fraction size 1.8 Gy. A total of six fractions of HDR ICR were given twice weekly with fraction size of 4 (3$\~$5.5) Gy to A point by Iridium-192 source. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. in vivo measurement of the rectal dose was peformed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 39 months, ranging from 6 to 90 months. Results: Twenty-one patients (9.5$\%$) experienced late rectal bleeding, from 3 to 44 months (median, 13 months) after the completion of RT. The calculated rectal doses were not different between the patients with rectal bleeding and those without, but the measured rectal doses were higher in the complicated patients. The differences of the measured ICR rectal fractional dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose was beyond 16 Gy, when the ratio of the measured rectal dose to A point dose was beyond 70$\%$, or when the measured rectal BED was over 110 Gy$_{3}$, a high possibility of late rectal complication was found. Conclusion: Late rectal complication was closely correlated with measured rectal dose by in vivo dosimetry using TLD during HDR ICR. If data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

• YAKHAK HOEJI
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• v.36 no.4
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• pp.291-302
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• 1992

Effects of Zinc chloride on the immune responses were studied in ICR mice. ICR male mice were divided into 5 groups(10 mice/group) and Zinc chloride at doses of 0.3, 1.2, 4.8 and 19.2 mg/kg were orally administered to ICR male mice once a day for three weeks. Mice were sensitized and challenged with sheep red blood cells(S-RBC). The results of this study were summarized as follows; (1) Zinc chloride significantly increased the body weight rate, the weight ratios of spleen and thymus to body weight and the number of circulating leukocyte, but significantly decreased them at the high dose of it, and increased dose-dependently the weight ratio of liver to body weight. (2) Zinc chloride significantly increased hemagglutination titer, Arthus reaction and plaque forming cell related to humoral immunity, but significantly decreased them at the high dose of it. (3) Zinc chloride significantly increased delayed-type hypersensitivity reaction and rosette forming cell related to cellular immunity, but significantly decreased them at the high dose of it. (4) Zinc choride significantly enhanced phagocytic activity, but significantly decreased according to the increase of its dose. These results suggest that high dose of zinc chloride decreased humoral, cellular and non-specific immune responses.

• Journal of Yeungnam Medical Science
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• v.5 no.1
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• pp.147-151
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• 1988

Esophageal cancers are highly malignant neoplasms. Prognosis of esophageal cancer treated by external irradiation alone is rather poor because of local recurrence and distant metastasis. Recently intracavitary irradiation has been used as a boost therapy after external irradation to optain better local control. One case of esophageal cancer has been treated by high dose rate remote-controlled afterloading unit as boost therapy after external irradiation. The result was excellent in short term follow up esophagogram but esophageal bleeding and esophagotracheal fistula were noted in further follow up examination after inappropriate posttreatment management including insufficient chemotherapy due to poor general condition. We reviewed possible causes of esophageal bleeding and esophagotracheal fistula after external irradiation and high dose rate ICR.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.181-189
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• 1995

Pupose: Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried We retrospectively analysed our experience of 122 patients. Comparision of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made Materials and Mathods: From January 1985 to December 1991 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined RT plus chemotherapy Mean age was 58 years(range:29-81). Histologic types were 111 squamous cell carcinoma, 5 large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage $IA(4.9\%),$ 11 had $IIA(9.0\%),$ 37 had $IIB(30.3\%),$ 3 had $IIIA(2.5\%),$ 63 had $IIIB(51.6\%).$ and 2 had stage $IV(1.6\%).$ In 77 patients with RT Plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleomycin, cisplatinum) , 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. Results: Complete response after external RT (3960cGy-5500cGy) was achieved in 61 patients$(50\%).$ The actuarial 5 year and 9 rear survival rate was $57.8\%\;and\;53.9\%,$ respectively. Five rear actuarial survival rate was $63.1\%$with RT alone(n=45) and $55.9\%$ with RT plus chemotherapy(n=77). The 5 rear survival rate was $35.5\%$ for 1 course of ICR and $67\%$ for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who were treated with 2 courses of ICR and dose to the A Point)=8000cGy (4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no difference in 5 year survival between 1 course and 2 course of ICR $(50\%\;vs\;56.8\%),$ and dose to point A less than 8000 cGy and more than 8000 $cGy(55.6\%\;vs\;55.7\%).$ There was no significant difference in survival between RT alone and RT plus chemotherapy for patients with tumor size greater than 3cm in size. Five year survival rate for early stage (Stage IB and IIA) with RT alone group and with RT Plus chemotherapy group was $60\%\;and\;77.0\%,$ respectively In advanced stage (stage IIB, IIIA, IIIB, IVA) the 5 year actuarial survival rate were $62.6\%,$ for RT alone group vs $53.6\%$ for RT plus chemotherapy group. Conclusion: Present study demonstrates that there is no survival advantage with adding chemotherapy in advanced stage of uterine cervix cancer. RT alone is considered as treatment of choice for patients with locally advanced cervix cancer. There was increased survival in RT alone group treated with RT dose above 8000 cGy to point A and 2 course of ICR. but 2 course of ICR and RT dose above 8000 cGy to point A did not affect survival advantage in RT plus chemotherapy group.

• Journal of Radiation Protection and Research
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• v.38 no.4
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• pp.166-171
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• 2013

While high-dose ionizing radiation results in long term cellular cytotoxicity, chronic low-dose (<0.2 Gy) of X- or ${\gamma}$-ray irradiation can be beneficial to living organisms by inducing radiation hormesis, stimulating immune function, and adaptive responses. During chronic low-dose-rate radiation (LDR) exposure, whole body of mice is exposed to radiation, however, it remains unclear if LDR causes changes in gene expression of the whole brain. Therefore, we aim to investigate expressed genes (EGs) and signaling pathways specifically regulated by LDR-irradiation ($^{137}Cs$, a cumulative dose of 1.7 Gy for total 100 days) in the whole brain. Using microarray analysis of whole brain RNA extracts harvested from ICR and AKR/J mice after LDR-irradiation, we discovered that two mice strains displayed distinct gene regulation patterns upon LDR-irradiation. In ICR mice, genes involved in ion transport, transition metal ion transport, and developmental cell growth were turned on while, in AKR/J mice, genes involved in sensory perception, cognition, olfactory transduction, G-protein coupled receptor pathways, inflammatory response, proteolysis, and base excision repair were found to be affected by LDR. We validated LDR-sensitive EGs by qPCR and confirmed specific upregulation of S100a7a, Olfr624, and Gm4868 genes in AKR/J mice whole brain. Therefore, our data provide the first report of genetic changes regulated by LDR in the mouse whole brain, which may affect several aspects of brain function.