• Radiation Oncology Journal
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• v.34 no.1
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• pp.64-75
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• 2016

Purpose: In order to evaluate the relationship between the dose to the liver parenchyma and focal liver reaction (FLR) after stereotactic ablative body radiotherapy (SABR), we suggest a novel method using a three-dimensional dose distribution and change in signal intensity of gadoxetate disodium-gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) hepatobiliary phase images. Materials and Methods: In our method, change of the signal intensity between the pretreatment and follow-up hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was calculated and then threshold dose (TD) for developing FLR was obtained from correlation of dose with the change of the signal intensity. For validation of the method, TDs for six patients, who had been treated for liver cancer with SABR with 45-60 Gy in 3 fractions, were calculated using the method, and we evaluated concordance between volume enclosed by isodose of TD by the method and volume identified as FLR by a physician. Results: The dose to normal liver was correlated with change in signal intensity between pretreatment and follow-up MRI with a median $R^2$ of 0.935 (range, 0.748 to 0.985). The median TD by the method was 23.5 Gy (range, 18.3 to 39.4 Gy). The median value of concordance was 84.5% (range, 44.7% to 95.9%). Conclusion: Our method is capable of providing a quantitative evaluation of the relationship between dose and intensity changes on follow-up MRI, as well as determining individual TD for developing FLR. We expect our method to provide better information about the individual relationship between dose and FLR in radiotherapy for liver cancer.

• Journal of the Korean Society of Radiology
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• v.17 no.1
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• pp.123-129
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• 2023

The purpose of this study was to analyze differences in imaging quality and dose difference between intra-venous (IV) and intra-arterial (IA) liver dynamic computed tomography (CT). Herein, retrospective, blinded analysis was conducted to analyze signal-to-noise and contrast-to-noise ratios in cases of patients who underwent IV or IA liver dynamic CT for transarterial chemoembolization (TACE), an interventional procedure for hepatocellular carcinoma. The dose length product (DLP) value stored in Picture Archive and Communication System (PACS) was used to calculate the effective dose and thereby compare differences in the dose between the two methods. The mean liver and spleen signal to noise ratio (SNR) was greater in IV-liver dynamic CT than in IA-liver dynamic CT; however, contrast to noise ratio (CNR) was higher in IA-liver dynamic CT than in IV-liver dynamic CT. However, there were no differences in DLP and effective dose between the two methods. In conclusion, our findings showed that IA-liver dynamic CT showed a similar effective dose and superior CNR compared with IV-liver dynamic CT. Further studies must analyze 3D angiography CT of the hepatic artery to clearly distinguish the feeding artery, which is the essential step in interventional procedures for hepatocellular carcinoma.

• The Korean Journal of Emergency Medical Services
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• v.10 no.1
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• pp.51-60
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• 2006

Background: The toxicity of paraquat has been known to be caused by oxygen free radicals which leads to the lipid peroxidation and multiple organ failure. High dose vitamin C has been known to be a effective antioxidant activities against the paraquat intoxication. This study was designed to evaluate the effect of regular injection of high dose vitamin C on liver damage in paraquat poisoned rat model. Method: Fifty five rats of Sprague-Dawley strain were divided into three groups: control group, only intraperitoneally injected saline; paraquat group, single dose intraperitoneally injected paraquat(24.5%, 40 mg/kg) and every 8 hours injected saline; paraquat and vitamin C group, single dose intraperitoneally injected paraquat(24.5%, 40 mg/kg) and every 8 hours injected vitamin C(72 mg/kg). Rats were sacrificed on the 12 hours, 1st day, 2nd day, 4th day, 7th day after injection and liver tissue was obtained. H&E(Hematoxylin & Eosin) stain and Masson's trichrome stain for collagen fiber detection were undertaken. The results were observed using the microscope. Results: 1. There were no differences between control and experimental group at the 12hours after regular injection of high dose vitamin C. 2. There were significantly decreased liver damage in experimental group in the 1st day after regular injection of high dose vitamin C. 3. There were significantly increased recovery of liver damage with time in experimental group after regular injection of high dose vitamin C. Conclusion: These results suggest that regular injection of high dose vitamin C is effective in decreasing liver damage in paraquat intoxication.

• Toxicological Research
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• v.11 no.2
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• pp.267-271
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• 1995

A single large dose of ethanol as well as chronic ethanol consumption produces alcoholic fatty liver in human and experimental animals. We examined the effects of YH439, a potential hepatoprotective agent, on alcoholic fatty liver generation in adult female rats. In rats treated with YH439 (250 mg/kg, po) 4 hr prior to a single dose of ethanol (6 g/kg, po), a significant decrease in hepatic triglyceride accumulation was observed. YH439 also has an inhibitory effect on hepatic triglyceride and cholesterol accumulation induced by repeated ethanol treatments for one week. Because it has been known that induction of alcoholic fatty liver is associated with lipid peroxidation and/or hepatic glutathione depression, the effect of YH439 on these parameters was determined in the livers of rats treated with ethanol. Coadministration with YH439 inhibited MDA formation and gIutathione depression induced by acute or repeated ethanol administration. In order to determine the effect of YH439 on ethanol metabolism in vivo, disappearance of ethanol from blood was measured. In rats treated with a single dose of ethanol (6 g/kg, po), the ethanol concentration in blood reached a peak approximately 120 min following the treatment which declined linearly for 18 hrs. YH439 had no effect on the decline of blood ethanol concentration regardless of the dose of ethanol given to rats. These results in this study suggest that YH439 has an inhibitory effect on fatty liver generation induced by acute or repeated ethanol consumption through a mechanism not directly related to the rate of ethanol metabolism in vivo.

• Herbal Formula Science
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• v.13 no.1
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• pp.123-143
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• 2005

Objective : This study was carried out to evaluate the liver toxicities of Wild Aconiti Tuber decoction. Methods : The amounts of aconitine in the methanol extract of Wild Aconiti Tuber was measured by HPLC. Safeties was studied by LD50 in mice. Liver toxicities were evaluated histologically and by CBC, blood chemistry after 2 weeks of 0.4g/kg/day clinical dosage oral administrations in rat. Results : 1. The amounts of aconitine in the methanol extract of Wild Aconiti Tuber is $1.697{\pm}0.052mg/g$. But aconitine was not detected in the water decoction of Wild Aconiti Tuber. 2. To evaluate LD50 and safeties of Wild Aconiti Tuber decoction, ICR mice were given high dose of 2, 5, 10g/kg for single time and were observed for 2 weeks. There were no dead animal and abnormal clinical sign and no abnormalities at the autopsy. So, LD50 was admitted to higher than 10g/kg. 3. After 2 weeks of 0.4g/kg/day clinical dosage oral administrations in rat, there was no significant change in the CBC and blood chemistry. 4. In the liver tissues of clinical dosage, mitotic figures, apoptosis and individual cell death were observed, but clear liver toxicities like fatty liver or necrosis were not observed. the liver tissues of high dose in mice, hydropic changes were getting severe as dose grows. Conclusions : According to the results, though aconitine was not detected in the Wild Aconiti Tuber decoction, 0.4g/kg/day 2 weeks p. o (clinical dosage) group showed weak changes in the liver tissues and high dose group showed liver toxicities like hydropic changes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1589-1593
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• 2012

Objective: To investigate liver fibrosis, TGF-${\beta}1$ levels and curative effects on hepatocellular carcinoma (HCC) with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE). Methods: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent super-selective transcatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21) chemotherapy groups. Results: With conventional doses, four indices of liver fibrosis focusing on hyaluronate acide (HA), human procollagen type-III (hPC-III), collagen type-Ⅳ (Ⅳ-C) and transforming growth factor-${\beta}l$ (TGF-${\beta}1$) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with small doses there were no significant differences except for TGF-${\beta}1$. Five year survival demonstrated no significant differences between the two groups (P>0.05). Conclusion: To hepatocellular carcinoma patients treated by TACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on five year survival.

• Journal of Preventive Medicine and Public Health
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• v.26 no.2 s.42
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• pp.231-250
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• 1993

Thirty five male Sprague-Dawley rats were treated with cadmium chloride solution ranging from 0.2 to 3.2mg $CdCl_2/kg$ by intravenous single injection. At 48 hours after administration of cadmium, total cadmium, MT bound cadmium and histopathologic finding in liver, kidney, lung, heart, testis, metallothionein in liver, kidney and total cadmium in bleed were examined. Tissue cadmium concentration was highest in liver, followed by in kidney, heart, lung and testis. Cadmium bound to rnetallothionein (MT-Cd) and ratio of MT-Cd to total cadmium were increased in liver and kidney dependently of cadmium exposure dose, but not significantly changed in other organs. On histopathologic finding, the most susceptible organ was heart in considering cadmium exposed dose, but testis in considering cadmium concentration. Blood cadmium concentration was increased with dose-dependent pattern, and significantly correlated with tissue cadmium concentration, so that we may estimate tissue cadmium concentration by measurement of blood cadmium concentration. Metallothionein in liver and kidney was increased with dose-dependent pattern, higher in liver than in kidney, and was significantly correlated with tissue cadmium concentration. However, metallothionein induction efficiency of tissue cadmium(${\mu}g\;MT/{\mu}g\;Cd$) was eater in liver than in kidney, and reverse to tissue concentration or exposed dose of cadmium.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1597-1602
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• 2014

The purpose of this study was to investigate whether whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases. From January 2007 to December 2012, 19 patients who exhibited massive (with a longest diameter > 5 cm) and invasive liver metastases and multiple metastases were treated with radiotherapy and concurrent chemotherapy. The total radiation dose was 53.4 Gy (range 38.8 Gy-66.3 Gy). All of the patients received a continuous intravenous dose of 5 fluorouracil (5-FU) 225 mg/m2 concurrently with radiation. The median survival time was 19 months. The 1- and 2- year overall survival rates were 78.3% and 14.3%, respectively. Of all of the patients who presented with abdominal pain, 100% experienced a decrease in pain. Decreases in the rates of ascites and jaundice were confirmed by ultrasound and bilirubin levels. No cases of Grade 4 or 5 acute or late toxicity were recorded. There were only two cases of Grade 3 toxicity (elevated bilirubin). These data provide evidence that whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases.

• Journal of Radiation Protection and Research
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• v.40 no.1
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• pp.25-35
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• 2015

We analyzed the differential effects of histopathology, apoptosis and expression of radiation response genes after chronic low dose rate (LDR) and acute high dose rate (HDR) radiation exposure in spleen, lung and liver of rats. Female 6-week-old Sprague-Dawley rats were used. For chronic low-dose whole body irradiation, rats were maintained for 14 days in a $^{60}Co$ gamma ray irradiated room and received a cumulative dose of 2 Gy or 5 Gy. Rats in the acute whole body exposure group were exposed to an equal dose of radiation delivered as a single pulse ($^{137}Cs$-gamma). At 24 hours after exposure, spleen, lung and liver tissues were extracted for histopathologic examination, western blotting and RT-PCR analysis. 1. The spleen showed the most dramatic differential response to acute and chronic exposure, with the induction of substantial tissue damage by HDR but not by LDR radiation. Effects of LDR radiation on the lung were only apparent at the higher dose (5 Gy), but not at lower dose (2 Gy). In the liver, HDR and LDR exposure induced a similar damage response at both doses. RT-PCR analysis identified cyclin G1 as a LDR-responsive gene in the spleen of rats exposed to 2 Gy and 5 Gy gamma radiation and in the lung of animals irradiated with 5 Gy. 2. The effects of LDR radiation differed among lung, liver, and spleen tissues. The spleen showed the greatest differential effect between HDR and LDR. The response to LDR radiation may involve expression of cyclin G1.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.1-7
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• 2010

Objectives: To introduce to TKM scientific dose conversion methods of human to animal or animal to human for new drug investigations. Methods: We searched guidelines of the FDA and KFDA, and compared them with references for drug-dose conversion from various databases such as PubMed and Google. Then, we analyzed the potential issues and problems related to dose conversion in safety documentation of new herbal drugs based on our experiences during Investigational New Drug (IND) applications of TKM. Results: Dose conversion from human to animal or animal to human must be appropriately translated during new drug development. From time to time, investigators have some difficulty in determining the appropriate dose, because of misunderstandings of dose conversion, especially when they estimate starting dose in clinical or animal studies to investigate efficacy, toxicology and mechanisms. Therefore, education of appropriate dose calculation is crucial for investigators. The animal dose should not be extrapolated to humans by a simple conversion method based only on body weight, because many studies suggest the normalization method is based mainly on body surface area (BSA). In general, the body surface area seems to have good correlation among species with several parameters including oxygen utilization, caloric expenditure, basal metabolism, blood volume and circulating plasma protein. Likewise, a safety factor should be taken into consideration when deciding high dose in animal toxicology study. Conclusion: Herein, we explain the significance of dose conversion based on body surface area and starting dose estimation for clinical trials with safety factor.