• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1845-1849
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• 2014

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 $mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 $mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.224-231
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• 2000

$Nokyangbotang^{TM}$ (NYBT) is a kind of powerful food for health and have been drunk at a oral dose of 80 ml (99.5 mg) three times per day: It has not been well studied about the anti-fatigue and hepatoprotective activity. In this experiments, we evaluated pathophysiologically the effect of NYBT on swimming time in mouse and hepatoprotective activity in rats intoxicated with carbon-tetrachloride. NYBT was nontoxic in orally acute toxicity test ($LD_{50}$, 320 ml/60 kg): a nontoxic food in more four times of one-shoot dosage (80 ml) to human. Weight-loaded forced swimming test was carried out to measure the swimming time of mice with a 4% load of body weight in plastic cylinder (diameter $10{\;}cm{\;}{\times}{\;}height{\;}20{\;}cm$) on water bath at $25^{\circ}C$, and the anti-fatigue activity represented the ratio of swimming time of experimental group to that of control group. NYBT had dose-dependent anti-fatigue activity Mice administered NYBT at a dose of 320 ml/60 kg once daily for 5 days could swim about two times more than control. Hepatoprotective activities of NYBT were examined by the determination of malonedialdehyde (MDA) and pathological survey in liver and liver function test of rat intoxicated with $CCl_4$ at i.m. dose of 2 ml/kg once daily for 7days. NYBT decreased dose-dependently thiobarbituric acid reactive substance: Oral administration of NYBT at a dose of 20 ml/60 kg was $38.51{\;}{\pm}{\;}3.02$ nmol MDA/g of tissue, that of 80 ml/60 kg was $33.76{\;}{\pm}{\;} 1.84$ nmol MDA/g of tissue, and that of 320 ml/60 kg was $32.87{\;}{\pm}{\;}1.90$ nmol MDA/g of tissue as compared with control group ($43.61{\;}{\pm}{\;}2.85$ nmol MDA/g of tissue). All rats administered NYBT at a dose of 320 ml/60 kg were survival as compared with 40% survival of control animals, and GPT activity of rats administered NYBT at a dose of 80 ml/60 kg was decreased as compared with control. In histopathological survey, NYBT improved slightly the fatty changes of hepatocytes around centrilobular area. These results suggest that NYBT has anti-fatigue and hepatoprotective activity in rats and mice.

• Korean Journal of Environmental Agriculture
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• v.10 no.2
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• pp.167-177
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• 1991

O-ethyl S-methyl ethylphosphonothioate [$LD_{50}$ (rat, oral) 4.6mg/kg ; $K_i$(bovine erythrocyte acetylcholinesterase) 303 $M^{-1\;min-1}$] was selected as a model compound to study the mode of action of O, S-dialkyl alkylphosphonothioates which have been hypothesized to be toxic via a bioactivation process. Two chemical oxidants, meta-chloroperoxybenzoic acid and monoperoxyphthalic acid, and rat liver microsomal oxidases were used to mimic the action of mixed function oxidases on the model compound. The formation of S-oxide, a very unstable active intermediate, was proposed based on the identification of metabolic products.Furthermore, a trapping experiment with ethanol showed that the unstable intermediate S-oxide had the ability to phosphorylate acetylcholinesterase which is an important enzyme in nerve systems. The S-oxide intermediates are presumed to be responsible for the toxicity of O,S-dialkyl alkylphosphonothioates.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.87-93
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• 1998

The tannic acid (0.5 mg/ml, 1.0 mg/mi, 2.0 mg/ml) and/or cadmium (20 mg/kg) were administered by oral administration. The results were as follows: 1. There were adverse effects on the weight changes and water consumption. But, the extent of adverse changes were decreased by tannic acid administration. 2. Also, there were some significant changes in organ weight, especially relative liver weight and relative brain weight by cadmium administration, but Ta1.0 group was significant changes in relative liver weight, relative lung weight and relative thymus weight compared with control group. 3. In the hematological patterns of administered mice, there were significant changes between cadmium treated groups and control group. Hemoglobin contents, packed cell volume, platelet count and neutrophill count were significantly change compared with control group. These changes were not shown in tannic acid treated group. 4. There were serological enzymatic changes in the cadmium treated mouse. In the tannic acid treated group 0.5, 1.0, 2.0 mg/ml, ALT, AST, BUN and creatinine were recovered to the extent of control group. From the above results, the tannic acid has some possible alleviative effects of cadmium toxicity upto the 2.0 mg/ml/day of oral dose for 4 weeks. But we need further study of mechanism for toxicty alleviating action of tannic acid to the heavy metals like cadmium.

• Tuberculosis and Respiratory Diseases
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• v.73 no.2
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• pp.93-99
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• 2012

Background: Local adverse events associated with inhaled corticosteroid use, including dysphonia, pharyngitis and oral candidiasis, can affect adherence for treatment. 'Mouth rinsing method' has been used for reducing local adverse events, but it cannot ensure complete prevention. The goal of this pilot study was to identify whether the 'immediate diet method' can reduce local adverse events in a limited number of patients. Methods: The study was conducted in a total of 98 patients, who had been prescribed a medium-dose fluticasone propionate for the first time, from January to October in 2010. One training nurse had performed the education on how to use the inhaler, including the mouth rinsing method. And with follow-ups at one month intervals, any patient who experienced such adverse events were educated on the immediate diet method, having a meal within 5 minutes after using an inhaler and they were checked on any incurrence of adverse events with one month intervals for 2 months. Results: The mean age of patients was 65.9 years old. The local adverse events had incurred from 18.4% of the study subjects. When performed the follow-up observation in 18 patients with local adverse events after education on the immediate diet method, 14 patients (77.8%) had shown symptomatic improvements. Three of 4 patients did not show any improvement, in spite of implementing the immediate diet method. The other 1 patient did not practice the immediate diet method properly. Conclusion: The immediate diet method may be useful in reducing the local adverse events, caused by the use of inhaled corticosteroid.

• Journal of dental hygiene science
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• v.12 no.3
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• pp.253-258
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• 2012

Dental amalgam is an alloy composed of a mixture of approximately equal parts of elemental liquid mercury and an alloy powder. Amalgam has been the most popular and effective restorative material used in dentistry. Despite the long history and popularity of dental amalgam as a restorative material, there have been periodic concerns regarding the potential adverse health effects arising from exposure to mercury in amalgam. Since children are more at risk for mercury toxicity, we aimed to assess the association between dental amalgam filling and urinary mercury concentration in children. 581 of elementary school children in grades 1st4th were conveniently recruited from two schools located in Daegu city, Korea. To obtain dental caries experience states, oral examination were conducted using the full term for DFS index, number of amalgam filling surfaces and the type of filling materials. A questionnaire was used to collect information about general characteristics and the frequencies of tooth brushing, gum chewing and fish/seafood consumption. The statistical analysis was done using the SPSS 18.0 program. The mean urinary mercury concentration in children having more surfaces was highest. As a results Urinary mercury concentration of children who have 79 teeth of amalgam filling and more than 10 is higher than without amalgam filling. The number of amalgam filling surface is closely related with urinary mercury concentration.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Fisheries and Aquatic Sciences
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• v.24 no.10
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• pp.330-339
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• 2021

Oyster (Crassostrea gigas) is a marine bivalve mollusk widely distributed in coastal areas, and have been long widely used in industrial resources. Several studies demonstrated that fermented oyster (FO) extract attribute to bone health, but whether administration of FO play as an endocrine disruptor has not been studied. Therefore, in the present study, we investigated the effect of FO on the endocrine system in vitro and in vivo. As the results of the competitive estrogen receptor (ER) and androgen receptor (AR) binding affinities, FO was not combined with ER-α, ER-β, and AR. However, 17β-estradiol and testosterone, used as positive control, were interacted with ER and AR, respectively. Meanwhile, oral administration of 100 mg/kg and 200 mg/kg of FO doesn't have any harmful effect on the body weight, androgen-dependent sex accessory organs, estrogen-dependent-sex accessory organs, kidney, and liver in immature rats. In addition, FO supplementation has no effect on the serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and 17β-estradiol. However, the relative weight of androgen- and estrogen-dependent organs were significantly increased by subcutaneously injection of 4.0 mg/kg of testosterone propionate (TP) and by orally administration of 1.0 ㎍ of 17α-ethynyl estradiol (EE) in immature male and female rats, respectively. Furthermore, TP and EE administration markedly decreased the serum LH and FSH levels, which are similar those of mature Sprague-Dawley (SD) rat. Furthermore, the testosterone and 17β-estradiol levels were significantly enhanced in TP and EE-treated immature rats. Taken together, our findings showed that FO does not interact with ER and AR, suggesting consequentially FO does not play as a ligand for ER and AR. Furthermore, oral administration of FO did not act as an endocrine disruptor including androgenic activity, estrogenic activity, and abnormal levels of sex hormone, indicating FO may ensure the safety on endocrine system to develop dietary supplement for bone health.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.87-94
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• 2008

In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells. The cells were cultured in various concentrations of CBD for 48 h and 25 ${\mu}$M of CBD for 6-36 h. The cells were observed to exhibit inhibitory effects of the cell viability in their growth, and then cytotoxicity was estimated. The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines. Also, to assess the membrane toxicity induced by CBD, we investigated lactate dehydrogenase (LDH) release. After treatment with various concentrations of CBD, LDH release rate of cancer cells was accelerated. On the other hand, in the induction of cell death, caspase-3, -8 and -9 activations were detected in cancer cells after treatment with various concentrations of CBD, and CBD effectively induced activity of caspase-3, -8 and -9 in A549 lung cancer cells, MDAMB-231 breast cancer cells and Renca kidney cells. Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 ${\mu}$M concentration.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7309-7313
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• 2015

Background: The organ preservation approach of choice for the treatment of locally advanced head and neck cancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacious treatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaks and increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy of concurrent chemoradiation using 40 mg/m2 weekly cisplatin. Materials and Methods: This is a single institutional retrospective study including the data of 266 locally advanced head and neck cancer patients who were treated with concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-value of < 0.05 was taken to be significant statistically for all purposes in the study. Results: The mean age of the study patients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatment time was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors, 3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of the study patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles of weekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional control and disease free survival. Conclusions: Concurrent chemoradiotherapy with moderate dose weekly cisplatin is an efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which can be used in developing countries with limited resources.