As currently conducted, standard rodent bioassays do not provide sufficient information to assess carcinogenic risk to humans at doses thousands of times below the maximum tolerated dose. Recent analyses indicate that measures of carcinogenic potency from these tests are restricted to a narrow range about the maximum tolerated dose and that information on shape of the dose-response is limited in experiments with only two doses and a control. Extrapolation from high to low doses should be based on an understanding of the mechanisms of carcinogenesis. We have postulated that administration of the maximum tolerated dose can increase mitogenesis which, in turn. increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because about half of all chemicals tested are indeed rodent carcinogens, and about 40% of the positives are not detectably mutagenic. Thus, at low doses where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than commonly assumed. In contrast, for high-dose exposures in the workplace, assessment of hazard requires comparatively little extrapolation. Nevertheless. permitted workplace exposures are sometimes close to the tumorigenic dose-rate in animal tests. Regulatory policy to prevent human cancer has primarily addressed synthetic chemicals, yet similar proportions of natural chemicals and synthetic chemicals test positive in rodent studies as expected from an understanding of toxicological defenses, and the vast proportion of human exposures are to natural chemicals. Thus, human exposures to rodent carcinogens are common. The natural chemicals are the control to evaluate regulatory strategies, and the possible hazards from synthetic chemicals should be compared to the possible hazards from natural chemicals. Qualitative extrapolation of the carcinogenic response between species has been investigated by comparing two closely related species: rats and mice. Overall predictive values provide moderate confidence in interspecies extrapolation; however, knowing that a chemical is positive at any site in one species gives only about a 50% chance that it will be positive at the same site in the other species.
Yang, Andrew Jihoon;Choi, Seo Hee;Byun, Hwa Kyung;Kim, Hyun Ju;Lee, Chang Geol;Cho, Jaeho
Radiation Oncology Journal
/
v.37
no.3
/
pp.193-200
/
2019
Purpose: To explore the role of salvage radiotherapy (RT) for recurrent thymoma as an alternative to surgery. Materials and Methods: Between 2007 and 2015, 47 patients who received salvage RT for recurrent thymoma at Yonsei Cancer Center were included in this study. Recurrent sites included initial tumor bed (n = 4), pleura (n = 19), lung parenchyma (n = 10), distant (n = 9), and multiple regions (n = 5). Three-dimensional conformal and intensity-modulated RT were used in 29 and 18 patients, respectively. Median prescribed dose to gross tumor was 52 Gy (range, 30 to 70 Gy), with equivalent doses in 2-Gy fractions (EQD2). We investigated overall survival (OS), progression-free survival (PFS), and patterns of failure. Local failure after salvage RT was defined as recurrence at the target volume receiving >50% of the prescription dose. Results: Median follow-up time was 83 months (range, 8 to 299 months). Five-year OS and PFS were 70% and 22%, respectively. The overall response rate was 97.9%; complete response, 34%; partial response, 44.7%; and stable disease, 19.1%. In multivariate analysis, histologic type and salvage RT dose (≥52 Gy, EQD2) were significantly associated with OS. The high dose group (≥52 Gy, EQD2) had significantly better outcomes than the low dose group (5-year OS: 80% vs. 59%, p = 0.046; 5-year PFS: 30% vs. 14%, p=0.002). Treatment failure occurred in 34 patients; out-of-field failure was dominant (intra-thoracic recurrence 35.3%; extrathoracic recurrence 11.8%), while local failure rate was 5.8%. Conclusion: Salvage RT for recurrent thymoma using high doses and advanced precision techniques produced favorable outcomes, providing evidence that recurrent thymoma is radiosensitive.
Gourd seeds were irradiated with the doses of 0-20 Gy to investigate the effect of the low dose $\gamma$-radiation on the early growth and physiological activity. The stimulating effects of the low dose y- radiation on the early growth were not noticeably high, but were increased generally at 4-16 Gy irradiation group. The catalase and peroxidase activity of cotyledon from seeds irradiated with $\gamma$- radiation were increased at 8 Gy irradiation group. The photochemical activity of leaf was noticeably high at 4 Gy irradiation group. The photochemical yield of PSII, estimated as Fv/Fm, decreased with increasing illumination time by 50% after 4 hrs in the control and 8 Gy irradiation group, while Fo slightly increased. However, Fv/Em in the 4 Gy irradiation group decreased by 40% of inhibition, indicating that photoinhibition decreased by the low dose $\gamma$- radiation. Changes in the effective quantum yield of PSII, $\varphi_{PSII}$ and 1/Fo- l/Fm, a measure of the rate constant of excitation trapping by the PSII reaction center, showed similar pattern to Fv/Em. NPQ decreased by 70% after photoinhibitory treatment with showing similar pattern between the control and the irradiation group. These results showed the positive effect of low dose $\gamma$- radiation on the seedling growth and the reduction of photoinhibition in the 4 Gy irradiation group.
Kim Woo Chul;Kim Gwi Eon;Chung Eun Ji;Suh Chang Ok;Hong Soon Won;Cho Young Kap;Loh JK
Radiation Oncology Journal
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v.18
no.1
/
pp.32-39
/
2000
Purpose :The incidence of adenocarcinoma of the uterine cervix is low. Traditionally, Low Dose Rate (LDR) brachytherapy has been used as a standard modality in the treatment for patients with carcinoma of the uterine cervix. The purpose of this report is to evaluate the effects of the High dose rate (HDR) brachytherapy in the patients with adenocarcinoma of the uterine cervix compared with the LDR. : From January 1971 to December 1992, 106 patients of adenocarcinoma of uterine cervix were treated with radiation therapy in the Department of Radiation Oncology, Yonsei University with curative intent. LDR brachytherapy was carried out on 35 patients and 71 patients were treated with HDR brachytherapy. In LDR Group, 8 patients were in stage I, 18 in stage II and 9 in stage III. External radiation therapy was delivered with 10 MV X-ray, daily 2 Gy fractionation, total dose 40$\~$46Gy (median 48 Gy). And LDR Radium intracavitary irradiation was peformed with Henschke applicator, 22$\~$59 Gy to point A (median 43 Gy). In HDR Group, there were 16 patients in stage 1, 38 in stage II and 17 in stage III. The total dose of external radiation was 40$\~$61 Gy(median 45 Gy), daily 1.8$\~$2.0 Gy. HDR Co-60 intracavitary irradiation was peformed with RALS (Remote Afterloading System), 30 $\~$ 57 Gy(median 39 Gy) to point A, 3 times a week, 3 Gy per fraction. Conclusion : The 5-year overall survival rate in LDR Group was 72.9$\%$, 61.9$\%$, 45.0$\%$ in stage I, II, III, respectively and corresponding figures for HDR were 87.1$\%$, 58.3$\%$, 41.2$\%$, respectively (p>0.05). There was no statistical difference in terms of the 5-year overall survival rate between HDR Group and LDR Group in adenocarcinoma of the uterine cervix. There was 11$\%$ of late complication rates in LDR Group and 27$\%$ in HDR Group. There were no prognostic factors compared HDR with LDR group. The incidence of the late complication rate in HDR Group stage II, III was higher than that in LDR Group(16.7$\%$ vs. 31.6$\%$ in stage II, 11.1$\%$ vs. 35.3$\%$ In stage III, p>0.05). Although the incidence of radiation induced late complication rate was higher in HDR Group stage II and III patients than that in the LDR Group, statistical significance was not detected and within acceptable level. Conclusion : There was no difference in terms of 5-year survival rate and failure pattern in the patients with adenocarcinoma of the uterine cervix treated with HDR and LDR brachytherapy. Even late complication rates were higher in the HDR group It was an acceptable range. This retrospective study suggests that HDR brachytherapy seems to replace the LDR brachytherapy in the adenocarcinoma of the uterine cervix. However, further studies will be required to refine the dose rate effects.
This study aims to validate the dosimetric characteristics of Low Dose Rate (LDR) I-125 source Geant4-based Monte Carlo code. According to the recommendation of the American Association of Physicists in Medicine (AAPM) task group report (TG-43), the dosimetric parameters of a new brachytherapy source should be verified either experimentally or theoretically before clinical procedures. The simulation studies are very important since this procedure delivers a high dose of radiation to the tumor with only a minimal dose affecting the surrounding tissues. GEANT4 Monte Carlo simulation toolkit associated brachytherapy example was modified, adapted and several updated techniques have been developed to facilitate and smooth radiotherapy techniques. The great concordance of the current study results with the consensus data and with the results of other MC based studies is promising. It implies that Geant4-based Monte Carlo simulation has the potential to be used as a reliable and standard simulation code in the field of brachytherapy for verification and treatment planning purposes.
By optimizing the radiation protection the collective dose and individual dose could be reduced during YGN #4 $5^{th}$ outage in 2001. The collective doses for the two high radiation jobs decreased to 85% and 65% of expected doses. The proportion of workers with low dose (below 1mSv) exposure increased 4% while the proportion of workers with over 3mSv and 5mSv exposure are decreased to 2%, 1% respectively. But none is exposed over 8mSv for the annual dose. To aid decision of utilizing the robot, cost- benefit analysis was performed and reasonable point was proposed to use the robot. For the first time job, repeated ALARA meeting and mock up training were implemented to set up working procedure by identifying the trouble. To easily set up standard procedure, mockup process was videotaped and reviewed during ALARA meeting. Monitoring is a good approach to chase radiological working condition such as working time, dose rate. behavior of workers, especially for high radiation work. Those data were estimated and adjusted from the stage of work planning to mock up. At the stage of actual work the monitoring data were compared to the estimation and recorded to database. This database will not only be used as a powerful tool for dose optimization at the following outage but also as a guideline to dose constraint set up for optimization for each specific situation.
Purpose: To evaluate the extent of pain response and objective response to palliative radiotherapy (RT) for bone metastases from hepatocellular carcinoma according to RT dose. Materials and Methods: From January 2007 to June 2010, palliative RT was conducted for 103 patients (223 sites) with bone metastases from hepatocellular carcinoma. Treatment sites were divided into the high RT dose and low RT dose groups by biologically effective dose (BED) of 39 $Gy_{10}$. Pain responses were evaluated using the numeric rating scale. Pain scores before and after RT were compared and categorized into 'Decreased', 'No change' and 'Increased'. Radiological objective responses were categorized into complete response, partial response, stable disease and progression using modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria; the factors predicting patients' survival were analyzed. Results: The median follow-up period was 6 months (range, 0 to 46 months), and the radiologic responses existed in 67 RT sites (66.3%) and 44 sites (89.8%) in the high and low RT dose group, respectively. A dose-response relationship was found in relation to RT dose (p=0.02). Pain responses were 75% and 65% in the high and low RT dose groups, respectively. However, no statistical difference in pain response was found between the two groups (p=0.24). There were no differences in the toxicity profiles between the high and low RT dose groups. Median survival from the time of bone metastases diagnosis was 11 months (range, 0 to 46 months). The Child-Pugh classification at the time of palliative RT was the only significant predictive factor for patient survival after RT. Median survival time was 14 months under Child-Pugh A and 2 months under Child-Pugh B and C. Conclusion: The rate of radiologic objective response was higher in the high RT dose group. Palliative AT with a high dose would provide an improvement in patient quality of life through enhanced tumor response, especially in patients with proper liver function.
According to the results measured the respiratory quotient of Saccharomyces cerevisiae with neutron radiation by manometric direct method, the respiratory quotient of them was stimulated at the dose(7$\times$106N/$\textrm{cm}^2$/sec) of neutron radiation for 60 seconds, and was inhibited in each group irradiated at the high dose (7$\times$108N/$\textrm{cm}^2$/sec) of neutron. Its physiological effects influenced on neutron had relations with respiratory quotient, reproductive rate and fermentation in the curve of normal logarithmic phase. The multiple reactions which appeared in yeast, indicated that a great deal of physiological function were closely correlated with the irradiated dosage of neutron. The kinds of free amino acid in yeast irradiated with neutron were different from those of unirradiated yeast. The activityof dehydrogenase system accelerated the metabolic function of yeast irradiated at some low dose of neutron. By this results, it may demonstrate that the fact which the phenomena obtained in the stimulation of neutron possess its character for several generation, is dependent on the theory of mutation. Subsequently, it seemed reasonable certain dominant type of microorganisms.
Won-Ho Kim;Bo Ram Lee;Hey-Yun Kim;Minji Kim;Jin-Woo Kim
Journal of Korean Dental Science
/
v.16
no.2
/
pp.182-191
/
2023
Purpose: This study investigated the orthodontic tooth movement after weekly parathyroid hormone (PTH) injection in mongrel dogs and analyzes bone formation activity on the tension and pressure sides of the tooth movement in mongrel dogs. Materials and Methods: Three mongrel dogs were used in this study. The first premolar was extracted and orthodontic force using 150 g of closed coil springs between the canine and second premolar was applied. The low-dose PTH group (PTH_1) and high-dose PTH group (PTH_2) received weekly injections of 1.61 ㎍/kg and 3.23 ㎍/kg of PTH, respectively. The control group received weekly injections of 1 ml of saline. Clinical, histomorphometric analysis were carried out. Result: The orthodontic tooth movement was greatest in the PTH_2 group and the lowest in the control group. Fluorescence staining images showed higher bone remodeling on the tension side of the tooth movement in the PTH_1 and PTH_2 groups. PTH_2 group showed a thicker labeling band than the PTH_1 group. PTH_2 group showed the highest mineral apposition rate and bone formation rate, followed by the PTH_1 group and the control group. Conclusion: Weekly intermittent PTH injection, especially in the short-term and at higher doses with orthodontic force, successfully increased orthodontic tooth movement and bone remodeling in mongrel dogs.
As the real time multimedia service become more popular, the needs of transmission with low delay and high quality are getting more stronger. Among those video compression technologies, the rate control method dose an important role in getting the effective data transmitting and the high image quality. In this paper, we combined the feature of CBR and VBR coding methods to propose a new bit-rate control method witch allows each frame to generates bits in the defined fluctuation range and applies a scene change detection at a part of frame and also can maintain low-delay and high quality even if the perfect VBR transmission environment is not guaranteed. The experiment result shows the proposed algorithm provides more effective method than TMN8 in real time application.
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