• Radiation Oncology Journal
• /
• v.19 no.2
• /
• pp.118-126
• /
• 2001

Purpose : In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. Materials and Methods : From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was $48.2{\pm}7.9\;Gy$ in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at $4\~8$ weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. Results : An objective response was observed in 106 of 158 patients, giving a response rate of $67.1\%$. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only $29.2\%$ showed objective response in patients treated with dose less than 40 Gy, while $68.6\%\;and\;77.1\%$ showed major response in patients with $40\~50\;Gy$ and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Conclusion : Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.

• Environmental Analysis Health and Toxicology
• /
• v.31
• /
• pp.1.1-1.13
• /
• 2016

Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (A-bomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down's syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.

• Journal of the Korean Data and Information Science Society
• /
• v.25 no.5
• /
• pp.987-998
• /
• 2014

The primary purpose of this paper is to derive a benchmark dose lower limit (BMDL) of lead for the attention deficit/hyperactive disorder (ADHD) based on a longitudinal cohort data set which is referred to as CHEER data set. The CHEER data were recently recruited from the Ministry of Environment of S. Korea to investigate the effect of environment on children's health We first confirm the correlation of ADHD with the blood lead level using a linear mixed effect model. We report from the longitudinal characteristic of CHEER data that ADHD scores tend to have "regression to the mean". A dose-response curve of blood lead level with ADHD being the end point is derived and from this dose-response curve a few BMDLs are derived based on corresponding assumptions on the benchmark region.

• Radiation Oncology Journal
• /
• v.4 no.2
• /
• pp.89-97
• /
• 1986

Using as assay for jejunal crypt stem cell survival, dose-response curves for the reproductive capacity of crypt stem cells of mouse jejunum exposed to multifractionated gamma-ray irradiation (single, 2, 3, 4, 5, 8, 10, 12, and 16 fractions) were analyzed and single-dose survival curve of these cells was constructed. The following conclusion were drawn: 1) Survival curves for higher numbers of dose fractions were displaced to higher dose, and characterized by increasingly shallower slopes. 2) The single-dose survival curve had broad shoulder, Dq=460 cGy, remaining near-exponential over initial dose range 0 to 300 cGy, with initial slope 1Do=474 cGy. 3) At fractionated dose En the range of 180 to 450 cGy, the average recovered dose per fraction interval was approximately $50\%$ of the dose per fraction. 4) The value of $\alpha/\beta$ ratio by using of linear regression analysis for the reciprocal dose plots was 8.3 Gy which lied in the range of 6-14 Gy for early-reacting tissues. 5) The linear-quadratic model for dose-response formula offers valid approximations for at 1 doses to be used in radiotherapy, only two parameters to be determined, and considerable convenience in practical applications.

• Journal of Microbiology and Biotechnology
• /
• v.11 no.3
• /
• pp.524-528
• /
• 2001

The measurement of radiation response using simple and informative techniques would be of great value in studying the genetic risk following occupational, therapeutic, or accidental exposure to radiation. When patients receive radiation therapy, many suffer from side effects. Since each patient receives a different dose due to different physical conditions, it is important to measure the exact dose of radiation received by each patient to lessen the side effects. Even though several biological dosimetric systems have already been developed, there is no ideal system that can satisfy all the criteria for an idean dosimetric system, especially for low-dose radiation as used in radiation therapy. In this study, an SOS Chromotest of E. coli PQ37 was evaluated as a novel dosimeter for low-dose gamma-rays. E. coli PQ37 was originally developed to screen chemical mutagens using the SOS Chromotest-a colorimtric assay, based on the induction of ${\beta}$-galactosidase ue to DNA damage. The survival fraction of E. coli PQ37 decreased dose-dependently with an increasing dose of cobalt-60 gamma-rays. Also, a good linear correlation was found between the biological damage revealed by the ${\beta}$-galactosidase expression and the doses of gamma-rays. The expression of ${\beta}$-galactosidase activity that responded to low-dose radiation under 1 Gy was $Y=0.404+(0.089{\pm}0.3)D+(-0.018{\pm}0.16)D^2$ (Y, absorbance at 420 nm; D, Dose of irradiation) as calculated using Graph Pad In Plot and Excel. When a rabbit was fed with capsules containing an agar block embdded with E. coli PQ37 showed a linear response to the radiation doses. Accordingly, the results confirm that E. coli PQ37 can be used as a sensitive biological dosimeter fro cobalt-60 gamma-rays. To the best of our knowledge, this is the first time that a bacterium has been used as a biological dosimeter, especially for low-dose radiation.

• Radiation Oncology Journal
• /
• v.38 no.1
• /
• pp.35-43
• /
• 2020

Purpose: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). Materials and Methods: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. Results: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. Conclusion: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

• Radiation Oncology Journal
• /
• v.7 no.2
• /
• pp.213-225
• /
• 1989

An analysis has been made of two hundred seven patients who were treated at the department of Radiation Oncology of Korea University Hospital for lung cancer from January 1981 through December 1986. There were 137 patients of nonsmall cell carcinoma (137/207, 66%), 26 patients of small cell carcinoma (26/207, 12.5%) and 44 patients of unproven histology. By aims of treatment, there were 104 patients (104/207, 50%) treated for cure, 89 patients (89/207, 42.9%) for palliation and 14 patients treated postoperatively. In 22 out of 207 patients, chemotherapy was done with radiotherapy, 12 of which were patients with small cell carcinoma. Stage II patients were 49 (49/207, 23.6%), stage III patients were 157 (157/207, 75.8%) and one patient had an occult cancer The tumor was initial Iy measured by CAT scan and chest X-rays in the 165 (165/207, 79.7%) patients, among which 117 patients had tumor diameter more than 5cm and 48 patients less than 5cm. Radiation therapy was given with Cobalt 60 teletherapy unit and the treatment volume encompassed primary tumor and the mediastinum. For curative aim, daily tumor dose of 180 cGy was given up to the range of 5,400~6,120cGy/30~34F/6~7 week period and for palliative aim, daily tumor dose of 300 cGy was given up to the range of 3,600~4,500 cGy/12~15F/2~3 week period. Postoperatively, mediastinum was treated for total dose of 5,040 cGy/28F/5.5 week period. 123 patients (123/207, 59%) were followed up after completion of radiotherapy for 14 months to 7 years. Local tumor response to the irradiation was measured by chest X-ray taken at one month follow up and was evaluated for response rate, if they were regressed more than 50% or less than 50% of the initial tumor size. The treatment results were as follows; 1. The median survival time was 8.5 months and survival rates for 1 year, 2 year and 5 year was 25%, 3.5% and 1% of nonsmall cell lung ca of 74 evaluable patients. 2. More than 50% of local tumor response rate was obtained in about half of overall cases; 90.5% for small cell ca, 50% for squamous cell ca, 25% for adenoca and 57% for large cell ca. 3. Response rate more than 50% was seen in the 50% of the patient group with tumor diameter more than 5cm and in the 55% of those with tumor diameter less than 5cm. 4. By total raidation dose given, patient group which was given 5,400~6,120 cGy equivalent dose or higher showed tumor response rate more than 50% in 53% of the patients, whereas the group with dose less than 5,400cGy equivalent, in 25% of the patients. 5. Survival rate for 6 month, 1 year and 2 year was compared between the group of local tumor response rate more than 50% vs. group with response rate less than 50%; 74% vs. 43%, 33% vs, 23%, 10% vs. 1%, respectively. 6. Local failure was seen in 21%(44/207) of the patients, which occured mostly within 15 months after completion of radiation therapy. Distant metastases were seen in 49.7%(103/207) of the patients, of which 43 cases were found before initiation of radiotherapy. The most common metastatic sites were bone and brain. In this sutdy, 1 year,2 year and S year survival rates were somewhat poor compared to the other studies. It mainly seems to be due to the poor general status of the patients and the far-advanced stage of the disease. In nonsmall cell cancer patients who had limited local disease and had small primary tumor size, we observed better local response. In addition, dose higher than 6,000 cGy group showed better tumor control than lower dose group. Survival rate was better for the local control group. For imporvement of local control of the lung cancer and hence, the survival of the patients with lung cancer, proper radical radiotherapy with high dose for localized disease is needed. New modality of treatment such as high LET beam in radiation therapy or drugs for the advanced disease as well as early diagnosis is also needed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8553-8557
• /
• 2016

Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

• Journal of Chest Surgery
• /
• v.16 no.3
• /
• pp.281-288
• /
• 1983

Heparinization is an essential step in extracorporeal circulation for open heart surgery. But wide individual variation to heparin effect sometimes makes it difficult to anticoagulate safely or neutralize appropriately. Because the conventional set protocol of heparinization did not consider this individual variation, a new method of control of heparinization was proposed by Dr. Brian Bull in 1974. We compared the group in which a conventional set protocol was used [Control group] with the other in which a new protocol modified from that of Bull was used [ACT group], on the aspects of the dosages of heparin and protamine administered and postoperative bleeding. Our conventional protocol [Control group] consisted of: 1. Initial heparin was given at dose of 350U/Kg into the right atrium prior to bypass. 2. Additional heparin was given every hour during E.C.C., as much as a half of the Initial dose. 3. 600U of heparin was mixed into every 100ml. of priming solution. 4. The protamine dose was calculated by totalling the units of heparin given to the patient and giving 1 .8mg. of protamine per 100 units of heparin. ACT protocol [ACT group] consisted of: 1. Initial heparinization was same as that of conventional protocol. 2. ACT`s were checked before [A point] and 10 minutes after initial heparinization [B point]. With these 2 points, a dose response curve was drawn. 3. Heparin for the priming solution was same as in control group. 4. Every 30 minutes during E.C.C., ACT`s were checked with Hemochron [International Technidyne Corp.]. ACT between 450 and 600 seconds was regarded as safety zone. If ACT checked at a time was below 450 seconds, heparin dose was calculated on the dose-response curve to lengthen ACT to 480 seconds and was given into the oxygenator. 5. About 10 minutes before the term of E.C.C., ACT was checked to estimate the blood heparin level at the time. Then, protamine dose was calculated at dose of 1.Stag per 100 units of heparin. The calculated dose of protamine was mixed into 50 to lO0ml of 5% Dextrose Water and dripped intravenously during the period of 15 minutes. Compared these two groups mentioned above, results were obtained as follows: 1. Mean value of normal ACT checked with Hemochron on 30 preoperative patients was 124 seconds [range 95-145 sec.]. 2. Doses of heparin and protamine given to the patient were decreased in ACT group as much as 32.2% and 62.2% respectively. 3. Postoperative bleeding and transfusion were also decreased in ACT group in 60.5% and 67.1% respectively. 4. Our modified dose-response curve did not cause any problems in the control of heparinization. 5. Initial heparinization [Heparin 350U/Kg] was sufficient for the most patients until 60 minutes under extracorporeal circulation. 6. We used 1.5mg of protamine to neutralize 100 units of heparin. But smaller dose of protamine may be sufficient for appropriate neutralization.

• YAKHAK HOEJI
• /
• v.43 no.5
• /
• pp.682-688
• /
• 1999

Abuse liability of ephedrine was investigated by measurement of locomotor activity and self-administration in Sprague-Dawley rats. Locomotor activity was determined in rats treated with 3, 10 and 30 mg/kg ephedrine for 14 days. Self-administration by ephedrine (0.23, 1 and 2.3 mg/kg) was examined in food-trained rats. We also examined effect of dopamine receptor antagonist (spiperone, $30{\;}\mu\textrm{g}/kg$) on the ephedrine-induced response of self-administration. Body weight was not statistically difference between control and ephedrine treatment group, but locomotor activity was dose-dependently increased. Self-administration for ephedrine was decreased in the early response (day 1 and 2) but the response was increased by higher dose of ephedrine. Self-administration was decreased by dopamine receptor antagonist (spiperone). These data showed that ephedrine increased locomotor activity and induced response of self-administration, and the effects of ephedrine were partially related to the dopaminergic system, which suggest the ephedrine may have abuse liability.