• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4147-4152
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• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• Korean Journal of Veterinary Research
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• v.44 no.4
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• pp.507-513
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• 2004

Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.

• The Journal of the Convergence on Culture Technology
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• v.4 no.2
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• pp.161-169
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• 2018

This study aimed to evaluate seaweed polysaccharide extracts as a cosmetic material. To assess anti-microbial efficacy, Staphylococcus aureus (S. aureus) was treated with seaweed polysaccharide extracts and zones of inhibition were measured. In addition, the anti-inflammatory effect was confirmed in RAW 264.7cells, and seaweed polysaccharide extracts was applied to the dorsal skin of Sprague-Dawley (SD) rats to evaluate single-dose toxicity. As a results, seaweed polysaccharide extracts did not exhibit cytotoxicity at concentrations up to $1,000{\mu}g/mL$ in skin fibroblasts. Furthermore, when S. aureus was treated with 1% seaweed polysaccharide extracts, clear zones of $1.52{\pm}0.34cm$ formed, confirming sufficient anti-microbial activity. When RAW 264.7 cells were treated with seaweed polysaccharide extracts extract, nitric oxide (NO) production decreased in a concentration-dependent manner and the production of inflammation-related cytokines, such as interleukin 1 beta ($IL1{\beta}$), tumor necrosis factor alpha ($TNF{\alpha}$), and prostaglandin E2(PGE2), decreased. When seaweed polysaccharide extracts extract was applied at various concentrations to rats, symptoms did not change for more than 14 d, and there was no change in body or organ weights. In conclusion we found that seaweed polysaccharide extracts is not cytotoxic and has anti-microbial and anti-inflammatory effects. Therefore, it is suitable for use as a cosmetic material.

• Journal of Ginseng Research
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• v.23 no.4
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• pp.222-229
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• 1999

Histopathological study has been carried out to elucidate the protective effect of Korean red ginseng water extract (KRG-WE) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity in male guinea pigs. Forty male guinea pigs ($200{\pm}20g$) were divided into 4 groups: normal controls (group 1) received vehicle and saline; group 2 (single TCDD-treated) received TCDD (5 ${\mu}g/kg$, single dose) and saline; group 3 received KRG-WE (200 mg/kg, i.p.) for 2 weeks starting 1 week before TCDD-exposure; group 4 received same dose of KRG-WE for 7 days from the day of TCDD-exposure. Weights of liver, testis, kidney, spleen and lung of the TCDD-exposed guinea pigs were significantly decreased. Thymus was severely shrunken, thereby could not be distinguished from adipose tissue in group 2 animals. Focal interstitial inflammation and fibrosis were observed from the lung parenchyma of group 2 animals. Furthermore, moderate swelling of hepatocyte, diffused aggregates of hemosiderin-laden macrophages from the Prussian blue stained spleen, marked decrease in spermatogenesis, and pyknotic and degenerative changes in the renal tubules were observed from intestinal organs of group 2 animals. On the other hand, histopathological damage was moderately to markedly alleviated in groups 3 and 4, but pretreatment of KRG-WE was more effective than the simultaneous treatment. In particular, TCDD-induced testicular atrophy was significantly attenuated by KRG-WE (p<0.01). From these results, it could be suggested that Korean red ginseng might be a useful herb that prevented TCDD-induced toxicity on liver, testis, kidney and spleen.

• Fisheries and Aquatic Sciences
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• v.23 no.9
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• pp.26.1-26.9
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• 2020

Background: The study evaluated the effects of a butaphosphan and cyanocobalamin mixture on the immune system and stress in olive flounders, Paralichthys olivaceus. Methods: The mixture was intramuscularly injected into olive flounders at the current recommended dose. Furthermore, to determine the toxicity of overdose, a histological examination was performed after injection of 1-, 2-, and 4-fold higher than the recommended dose. Results: Immunity parameters were altered during the first 2 weeks after a single intramuscular injection of the mixture in olive flounders (average weight 20.5 ± 1.1 g). The levels of all tested items, except glutathione and antiprotease, were higher in the treated group than in the control group in the first week; the levels of all tested items were even higher in the second week in the treated group than in the control group. The level of nitro-blue tetrazolium, myeloperoxidase, and superoxide dismutase between the two groups differed significantly. Changes in the stress response to different seawater temperatures (increase or decrease in seawater temperature by 3-5 ℃ using 50 L heated or cooled seawater tanks) were studied by determining the changes in cortisol and glucose levels on days 1 and 7. Both cortisol and glucose levels were significantly lower in the treated group than in the control group. Histological analysis did not reveal any abnormalities after intramuscular injection of the mixture at doses that were 1-, 2-, and 4-fold higher than the recommended dose. Conclusions: Intramuscular injection of a butaphosphan and cyanocobalamin mixture is safe and effective in reducing stress and improving immunity in olive flounders.

• Toxicological Research
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• v.29 no.1
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Toxicological Research
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• v.22 no.2
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• pp.75-85
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• 2006

This study was designed to evaluate the possible DNA damaging effects of T-2 toxin using an alkaline single cell gel electrophoresis (SCGE) comet assay and also to investigate toxic effects in chickens. A total of 20 chickens were used in these experiments. Graded concentrations of dietary T-2 toxin (0, 4, 8, and $16{\mu}g/g$ of diet) were given to groups of 5 broiler chickens. In comet assay, The DNA damage was analysed by the tail extent moment (TEM) and tail length (TL), which were used as markers of DNA strand breaks in SCGE. A significant dose-dependent increase in the extent of DNA migration as well as in the percentage of cells with tails was observed after treatment with T-2 toxin (P<0.05). Treatment with the low T-2 toxin ($4{\mu}/g$ of diet) induced a relatively low level of DNA damage in comparison with the high T-2 toxin ($16{\mu}/g$ of diet) group. The growth rate was significantly reduced by concentrations of 8, and $16{\mu}/g$ of diet (P < 0.05). The feed conversion ratio were significantly affected by any concentrations (P < 0.05). The relative weight of the spleen, and lung was decreased by the growth inhibitory concentrations. The bursa of Fabricius, thymus, and kid- ney were decreased in relative weight by concentrations of $16{\mu}/g$ of diet. The relative weight of the liver and heart were unaffected. The hemoglobin (Hb), hematocrit (HCT), and mean corpuscular hemoglobin (MCH) were decreased at concentration of $16{\mu}/g$ of diet. As compared with control chickens, there was no marked change in serum components except uric acid in T-2 treated chickens. All lymphoid tissues retained atrophic and lymphoid cell depletion throughout the three weeks trial.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.310-319
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• 2015

Purpose: Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma that is highly sensitive to radiotherapy (RT). However, the effectiveness of RT has not been well established. We reviewed our experiences to assess the role of RT for FL and analyze treatment results. Materials and Methods: Retrospective analysis was done on 29 patients who received first RT between January 2003 and August 2013. Of 23 early stage (stage I, II) patients, 16 received RT alone, four received chemotherapy followed by RT, two received RT postoperatively, and one received salvage RT for relapse after resection. Six advanced-stage (stage III, IV) patients received RT after chemotherapy: two received consolidation RT, three received salvage RT for residual lesions, and one received RT for progressive sites. Median RT dose was 30.6 Gy (range, 21.6 to 48.6 Gy). Median follow-up duration was 62 months (range, 6 to 141 months). Results: All patients showed complete response in the radiation field. Eight outfield relapses were reported. Seven patients received salvage treatment (three chemotherapy, four RT). Four patients showed excellent responses, especially to RT. Estimated 5-year and 10-year relapse-free survivals were 72% and 60%. In the RT-alone group, 5-year relapse-free survival was 74.5%. All advanced-stage patients were disease-free with 100% 5-year overall survival. Disease-specific death was noted in only one patient; four others died of other unrelated causes. No significant toxicity was reported. Conclusion: RT resulted in excellent treatment outcomes for all FL stages when used as a primary treatment modality for early stage or salvage-treatment modality for advanced-stage disease.

• Korean Journal of Veterinary Research
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• v.16 no.1
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• pp.59-64
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• 1976

In the sequence of carbon tetrachloride hepatotoxicity, increased serum levels of a number of enzymes have been demonstrated in experimental animals. These observations, therefore, have served to help in detecting hepatic injury. The serological influence of chlorpromazine (CPZ) and iproniazid on the acute $CCl_4$ poisoning was executed in this investigation taking use of 6 albino rabbits (around 2 kg b.w.) in each group. By measuring of blood sugar level (Nelson-Somogyi method), S-GOT and S-GPT activities (Reitman-Frankel method), the pharmacological effects of the drugs was evaluated setting pretreated groups against the control. The results obtained were summarized as follows: 1. The intramuscular injection of $CCl_4$ led to increase the blood sugar level in first 3 hours and, after that, to decrease reasonably. But CPZ-pretreated group showed a tendency of increasing in compare with the control, and iproniazid-pretreated group inhibited evidently. 2. In S-GOT activity, the increased level was induced by $CCl_4$ in control. And CPZ-pretreated group showed a increased level until first day and decreased rapidly. But this property inhibited inhibited significantly by pretreating with iproniazid. 3. Although a single dose of $CCl_4$ increased the S-GPT activity, the more increasing trend was observed in CPZ-pretreated group. But these tendencies depressed remarkably in the iproniazid-pretreated group. It seemed to be attributed not to defend the $CCl_4$ toxicity but to be suppressed the enzyme systems in the liver by iproniazid that the blood sugar level and serum transaminase activities was decreased significantly in pretreating with iproniazid.

• Journal of Haehwa Medicine
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• v.22 no.1
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• pp.119-128
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• 2013

Objectives: Yijin-tang-gamibang has been used in the Korean Medicine for treating various digestive disease. This study was aimed to investigate the effects and safety of Yijin-tang-gamibang in reflux esophagitis through the analysis of articles. Method: A total of 9 articles about Yijin-tang-gamibang and reflux esophagitis were used to develop this article. Results: According to basic research and clinic research data, it is supported that Yijin-tang-gamibang was useful prescription in reflux esophagitis. Yijin-tang-gamibang has favorable protective effects on the reflux esophagitis induced by pylorus and forestomach ligation in rats. After treatment with Yijin-tang-gamibang, patients showed improvement in all symptoms associated with reflux esophagitis and functional dyspepsia, including general condition. And Yijin-tang-gamibang did not show any toxic effect in single oral dose toxicity test. Conclusion: The results of this study suggest that Yijin-tang-gamibang showed favorable protective effects on the reflux esophagitis. However, it proved insufficient to confirm its efficacy owing to lack of clinical studies of high quality. So, we need well designed studies to verify clinical efficacy of Yijin-tang-gamibang hereafter.