• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2771-2774
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• 2012

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

• Radiation Oncology Journal
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• v.4 no.1
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• pp.1-13
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• 1986

In order to clarify the effect of radiation on the mouse jejunal crypt cells by combined administration of administration and radiation and also to evaluate the enhancing effect of adriamycin, the authors performed this study by delivering single irradiation of 1,000 to 1,600 rad to the whole abdomen of mice by cobalt-60 teletherapy unit. In combination with adriyamycin treatment groups, the drug was administered as single dose of 10 mg/kg either 2 hours before or 4 hours after graded single dose,900 to 1,400 rad, of irradiation. The authors studied the quantitative changes of intestinal crypt cells by microcolony survival assay technique and the morphological changes of small intestinal villi by scanning electron microscope in mice following to combined therapy with adriamycin and irradiation, The average number of jejunal crypts per circumference was $130{\pm}16$ in control group. The mean lethal dose(Do) of each irradiation alone and combined therapy groups 2 hours before and 4 hours after irradiation, were 160, 170, and 170 rad in cell survival curves, respectively. The dose effect factor(DEF) of adriamycin in each groups of pre-irradiation and post-irradiation were 1.19 and 1.26, respectively. The conical shaped villi were noted on 1,200 rad in irradiation alone group and 1,000 rad in combined groups. For the proper clinical application we must be careful of the radiation injury to small bowel when the anticancer chemotherapy and radiation therapy to the abdomen and pelvic area are used as combined therapeutic modality.

• Toxicological Research
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• v.29 no.4
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• pp.263-278
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• 2013

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.1
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• pp.20-25
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• 2011

Purpose: This study was designed to analyze the contributing factors, as well as the incidence and nature of the cardiac toxicity, in patients presenting with diphenhydramine overdose. Methods: We retrospectively reviewed the medical records of the intoxicated patients who presented to the ED of Korea University Anam Hospital from January 2008 to December 2010. Those patients who visited due to a diphenhydramine overdose were selected and the following features were recorded for analysis: the general characteristics, vital signs, the amount of ingested diphenhydramine, the time interval from ingestion to presentation, the coingested drugs (if any), the toxicities and the ECG findings. Cardiac toxicity, while defined mainly in terms of the temporary ECG changes such as QTc prolongation, right axis deviation, QRS widening, high degree AV block and ischemic changes, also encompassed cardiogenic shock, which is a clinical finding. Results: A total of eighteen patients were enrolled. Of the eighteen patients, eight had ingested diphenhydramine only, while ten had ingested other drugs in addition to diphenhydramine. The most commonly observed toxicity following diphenhydramine overdose included cardiac toxicity (78%). Cardiac toxicity was observed in all the patients who presented to the emergency department 2 hours after ingestion. The patients with QTc prolongation turned out to have ingested significantly larger amounts of diphenhydramine. Conclusion: QTc prolongation and right axis deviation were common findings for the patients with a diphenhydramine overdose. QTc prolongation was more likely to occur with ingesting larger amounts of diphenhydramine. Close monitoring is mandatory for patients who have ingested large amounts of diphenhydramine to prevent such potentially lethal cardiac toxicity.

• Journal of fish pathology
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• v.23 no.3
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• pp.293-302
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• 2010

Effects of formalin on removal of Pseudodactylogyrus spp. were examined against naturally infected eel, Anguilla japonica (weight 89.9~96g) at a water temperature of $28^{\circ}$. Prior to experiments for removal of the parasite, the hematological toxicity of formalin bath at 0~500 ppm for 30 min~24 h was assessed by hematocrit values (Ht). Based on the results of Ht, appropriate methods of treatment, concentrations and durations, were examined in the main study. There was no significant (P>0.05) change of Ht in 100 to 200 ppm for 24 h. In contrast, Ht increased significantly (P<0.05) at above 300 ppm. This suggests that physiological damage was caused by formalin bath treating with 300 to 500 ppm. Formalin bath with 100 and 200 ppm for 24 h caused significant decreases (P<0.05) in the infection of the parasite. In conclusion, the 100 ppm formalin for 24 hour-bath was found most recommendable for the effective treatment of Pseudodactylogyrus spp. for the gills of the infected eel because of the median lethal concentration ($LC_{50}$) of formalin to eel; cumulative mortalities were found to be 0 and 13.3%, respectively, following 24 h bathing.

• Journal of Korean Philosophical Society
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• v.147
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• pp.261-281
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• 2018

This paper will cover recent discussions on the risks of human being due to the development of artificial intelligence(AI). We will consider AI research as artificial narrow intelligence(ANI), artificial general intelligence(AGI), and artificial super intelligence(ASI). First, we examine the risks of ANI, or weak AI systems. To maximize efficiency, humans will use autonomous AI extensively. At this time, we can predict the risks that can arise by transferring a great deal of authority to autonomous AI and AI's judging and acting without human intervention. Even a sophisticated system, human-made artificial intelligence systems are incomplete, and virus infections or bugs can cause errors. So I think there should be a limit to what I entrust to artificial intelligence. Typically, we do not believe that lethal autonomous weapons systems should be allowed. Strong AI researchers are optimistic about the emergence of artificial general intelligence(AGI) and artificial superintelligence(ASI). Superintelligence is an AI system that surpasses human ability in all respects, so it may act against human interests or harm human beings. So the problem of controlling superintelligence, i.e. control problem is being seriously considered. In this paper, we have outlined how to control superintelligence based on the proposed control schemes. If superintelligence emerges, it is judged that there is no way for humans to completely control superintelligence at this time. But the emergence of superintelligence may be a fictitious assumption. Even in this case, research on control problems is of practical value in setting the direction of future AI research.

• Korean journal of applied entomology
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• v.57 no.3
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• pp.221-231
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• 2018

The susceptibility of the western flower thrips, Frankliniella occidentalis and garden thrips, Frankliniella intonsa was evaluated using 51 commercial insecticides. 15 kinds of insecticides which showed more than 90% mortality against both thrips, F. occidentalis and F. intonsa was selected. Many active ingredients were misused and abused in commercial mixture formulation insecticides. Since the F. intonsa was more susceptible than F. occidentalis, it was considered that both thrips can be controlled by insecticides that showed insecticidal activity on the F. occidentalis. Lethal time ($LT_{50}$ and $LT_{95}$), systemic toxicity and residual toxicity of selected insecticides were compared. Both chlorpyrifos WP and chlorpyrifos + diflubenzuron WP revealed the fastest toxicity within 2 h ($LT_{95}$), while spinetoram WG revealed the slowest toxicity as 62.3 h ($LT_{95}$). Chlorfenapyr SC showed toxicity at foliar and drenching application while spinetoram WG was toxic only in foliar application. Chlorfenapyr SC showed residual effect at 3, 5, 7, 10, 15 days after treatment and both benfuracarb WG and chlorpyrifos WP showed residual effect at 3 days after treatment. As a result of treatment of selected insecticides for field population of F. occidentalis, the population collected from horticultural crops showed lower susceptibility than the population collected from vegetable crops.

• Proceedings of the Korea Society of Environmental Biology Conference
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• 2005.12a
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• pp.38-45
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• 2005

The egg bags of Korean salamander(Hynobius leechii) were collected from farmlands in Gyeongsangnam-do area. The assumed breeding time, numerical variation of embryos in each egg bag, mortality and the rates of abnormalities were investigated. The toxicity of benomyl, the metabolite carbendazim and BIC which were frequently spread in agricultural area and caused spontaneous embryonic malformation was investigated. The assumed breeding time between the end of February and the end of March has the difference about a month because of a habitat and it takes about 2 or 3 weeks from laying eggs to hatching. The length of each egg bag and the number of embryos were very varied in each area. It is due to geographical variation. Among egg bags in total study area, only 406 of egg bags(17.70% of total egg bags) developed all of embryos to normal larvae, and 78.49% of total embryos were normally developed. The patterns of spontaneous embryonic malformation were 26 species from A to Z and the abnormal patterns in individual were 8 species and above. the geographical differences about the abnormal pattern were identified and 11 habitats categorized 4 groups. The most frequent abnormality in Gyeongsangnam-do area is the dysplasia of external gill. The caudal dysplasia, abdominal blister and dysplasia of fin were also frequently observed. Individuals showing severe external defect were histologically studied and they showed retinal hypo-pigmentation, thyroid carcinoma, somatic muscular dysplasia, degeneration of cephalic neuron and various organ dysplasia. Benomyl and carbendazim were treated by 10pM$^{\sim}$10uM and BIC was treated by 1$^{\sim}$40ppm to know the effect of toxicity about toxic substance of salamander. After benomyl was treated, a survival rate was sharply dropped from 2 to 8 days. $LC_{100}$ identified in $1{\mu}M$, $LC_{50}$ identified between 100nM and $1{\mu}M$. $EC_{50}$ was assumed between 10nM and 100nM. The prevalent external malformation was abdomen swelled abnormally and histo-pathological effects were abdomen, neural tube and lens hernia. This suggests that benomyl is the toxicitic substance which inhibits the development of digestive system and nervous system. The result of treated carbendazim was similar to that of the treated benomyl. The survival rate is sharply dropped between 2 and 6 days. $LC_{100}$ was identified $1{\mu}M$ and $LC_{50}$ was identified between 10nM and 100nM. This shows that cabendazim has stronger lethal toxicity than benomyl. Ventral blister, eye dysplasia and cephalic dysplasia in the individual of external malformation mean that cabendazim affected nervous system much more than benomyl. Because the toxicity of BIC affected less in the beginning but affected more in the near hatching period, the period causing toxicity is somewhat different. $LC_{100}$ identified near 40ppm and $LC_{50}$ identified near 25ppm. The external defect shows mainly ventral blister and histo-pathological results show intestinal deformities. This result suggests the BIC inhibited strongly the development of digestive system. These abnormal developments may be caused by antimitotic action, inhibition of tubulin complex, destruction of microtubule, inhibitions of neurulation and closing of neural fold, and by the inhibition of movement of neural crest cells of benomyl. These abnormal developments may be caused by the rupture of epithelium, the loss of microtubule, the reduction of spindle size, the inhibition of spindle assembly formation, the destruction of spindle poles of carbendazim. These abnormal developments may be caused cytotoxicity by inhibition of the synthesis of a number of macromolecules and similar reaction the inhibition of benomyl.

• The Korean Journal of Mycology
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• v.46 no.3
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• pp.295-306
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• 2018

In the present study, we compared the effects of 50% ethanolic extracts of Chinese and Korean Wolfiporia cocos (CPE and KPE) on in vitro lipid accumulation in 3T3-L1 cells and their anticancer activities in Sarcoma 180 cells. We further compared the anticancer activities and the 50% inhibitory concentrations ($IC_{50}$) of CPE with KPE with cultivated for one and two years in a landfill and a facility (LPE and FPE), respectively. In addition, the single oral dose toxicities of CPE and KPE were evaluated in mice. Lipid accumulation was inhibited after 48 hours, in CPE and KPE treated 3T3-L1 cells; however, no significant difference was observed between CPE and KPE in their lipid accumulation inhibitory activities. The anticancer activity of KPE was higher than that of CPE at $300{\mu}g/mL$ (p<0.05), revealing the possibility of an auxiliary biological means for origin identification. The anticancer activities of LPE and FPE were significantly stronger than that of CPE (p<0.05) but there was no difference between extracts from one- and two-year-old W. cocos, irrespective of the cultivation method. In single oral dose toxicity tests, CPE and KPE did not induce mortality during the 14-day observation. Thus, the 50% of lethal dose ($LD_{50}$) of CPE and KPE were estimated to be higher than 2,000 mg/kg. Taken together, our results indicate that the anticancer assay could be an auxiliary means of identifying the origin of W. cocos. In addition, artificial cultivation could be an alternative way to reduce the import of W. cocos. Lastly, 50% ethanolic W. cocos extracts could be potential candidates for obesity and cancer managements.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.