Kim, Yeon-Sil;Roh, Kwang-Won;Chae, Soo-Min;Mun, Seong-Kwon;Yoon, Sei-Chul;Jang, Hong-Seok;Chung, Su-Mi
Radiation Oncology Journal
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v.25
no.4
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pp.233-241
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2007
Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstream signaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results suggest that a better predictor of radiation response would be inhibition of a crucial signaling pathway than inhibition of a receptor.
BACKGROUND: Mine drainage from metal mining districts is a well-recognized source of environmental contamination. Oxidation of metal sulfides in mines, mine dumps and tailing impoundments produces acidic, metal-rich waters that can contaminate the local surface water and soil. METHODS AND RESULTS: This experiment was carried out to investigate the pollution assessment of heavy metal on the water quality of mine drainage, paddy soils and sediment in lower watershed affected by mine drainage of the Sambo mine. The average concentrations of dissolved Cd (0.018~0.035 mg/L) in mine drainage discharged from the main waste rock dumps(WRD) was higher than the water quality standards (0.01 mg/L) for agricultural water in Korea. Also, the average concentrations of dissolved Zn, Fe and Mn were higher than those of recommended maximum concentrations (Zn 2.0, Fe 5.0, Mn 0.2 mg/L) of trace metal in irrigation water proposed by FAO (1994). The average contents of Pb and Zn in paddy soils was higher than those of standard level for soil contamination(Pb 200, Zn 300 mg/kg) in agricultural soil by Soil Environmental Conservation Act in Korea. Also, the concentrations of Cd, Pb and Zn in sediment were higher than those of standard level for soil contamination (Cd 10, Pb 400, Zn 600 mg/L) in waterway soil by Soil Environmental Conservation Act in Korea. The enrichment factor (EFc) of heavy metals in stream sediments were in the order as Cd>Pb>Zn> As>Cu>Cr>Ni. Also, the geoaccumulation index (Igeo) of heavy metals in stream sediments were in the order as Zn>Cd>Pb>Cu>As>Cr>Ni, specially, the geoaccumulation index (Igeo) of Zn (Igeo 3.1~6.2) were relatively higher than that of other metals in sediment. CONCLUSION(s): The results indicate that stream water and sediment were affected by mine drainage discharged from the Sambo mine at least to a distance of 1 km downstream (SN-1, SN-2) of the mine water discharge point.
The blood chemical values and blood enzyme activities were examined from 74 healthy mixed breed dogs in the area of Seoul. The results obtained are summarized as follows; 1. Mean${\pm}$SD values and ranges of glucose were $61.97{\pm}8.41mg/100ml$ and 47.28~81.67mg/100ml, of blood urea nitrogen(BUN) $15.99{\pm}2.31mg/100ml$ and 8.21~21.31mg/100ml, of total protein(TP) $8.17{\pm}0.93g/100ml$ and 6.06~9.91g/100ml, of albumin $4.16{\pm}0.47g/100ml$ and 2.81~5.15g/100ml, of globulin, $4.01{\pm}0.64g/100ml$ and 2.72~5.54g/100ml, of albumin/globulin(A/G) ratio $1.06{\pm}0.17$ and 0.71~1.42, of cholesterol(Chol) $187.33{\pm}19.78mg/100ml$ and 128.70~222.90mg/100ml, of total bilirubin(TB) $0.73{\pm}0.14mg/100ml$ and 0.43~1.16mg/100ml, of phosphorus(Pi) $5.25{\pm}1.00mg/100ml$ and 2.61~7.72mg/100ml, of calcium(Ca) $10.76{\pm}1.08mg/100ml$ and 8.24~12.60mg/100ml, of triglyceride(TG) $89.48{\pm}21.16mg/100ml$ and 47.80~133.00mg/100ml, respectively. 2. The glucose value in the age group of 7~12 months was higher (p<0.01) but in the age group of 3~4 years was lower (p<0.05) than the total glucose value. The TP value in the age group of 7~12 months was lower (p<0.01) but in the age group of 1~2 years was higher (p<0.05) than the total TP value. The globulin value in the age group of 7~12 months was lower (p<0.01) but in the group of 1~2 years was higher (p<0.01) than the total globulin value. The A/G ratio value in the age group of 7~12 months was higher (p<0.05) but in the age group of 1~2 years was lower (p<0.05) than the total A/G ratio value. The phosphorus values in the age group of 1~2 years and the age group of 3~4 years were lower (p<0.01, p<0.001) than the total phosphorus value. The calcium value in the age group of less than 6 months was higher (p<0.05) but in the age group of 7~12 months was lower (p<0.001) than the total calcium value. 3. Mean${\pm}$S.D. values and ranges of alkaline phosphatase(AP) were $72.47{\pm}19.73IU/l$, and 28.13~105.00IU/l, of lactic dehydrogense(LDH) $159.46{\pm}45.11IU/l$ and 60.63~265.30IU/l, of serum aspartate aminotransferase(AST) $38.64{\pm}8.62IU/l$ and 21.47~70.58IU/l, of serum alanine aminotransferase(ALT) $34.88{\pm}11.30IU/l$ and 14.51~73.17IU/l, respectively. 4. The AP value in the age group of 7~12 months was higher (p<0.05) but in the age group of 1~2 years was lower (p<0.01, p<0.001) than the total AP value. The LDH value in the age group of less than 6 months was higher (p<0.001) but in the age group of 1~2 years and the age group of 3~4 years were lower (p<0.05) than the total LDH value. The serum AST value in the age group of 3~4 years was lower (p<0.01) than the total SGOT value. The serum ALT value in the age group of 7~12 months was higher(p<0.05) than the total SGPT value.
Objectives: To evaluate the accuracy and consistency of two different apex locators at both the Apex and 0.5 marks. Materials and Methods: Twenty-six root canals was scheduled for extraction for periodontal or prosthodontic reasons. Thirteen canals were measured using Root ZX and the rest by i-ROOT. The root canal length was measured both the at 0.5 mark and the Apex mark. The file was then fixed to the toot, and the distance from the file tip to the major foramen of each canal was measured after removing the root dentin under the microscope so that the major foramen and the file tip were seen. Results: 1. When the Apex mark was used, 100% of both the Root ZX and i-ROOT groups were within 0.5 mm of the major foramen. 2. When 0.5 mark was used, 100% of the Root ZX group and 77% of the i-ROOT group were within 0.5 mm of the major foramen. 3. In terms of standard deviation and quartile value, the Apex mark was more consistent than 0.5 mark in the Root ZX group, and 0.5 mark was more consistent in the i-ROOT group, but there was no statistically significant difference when compared with t-test. 4. The root canal length difference between the Apex mark and 0.5 mark was 0.22 mm and 0.46 mm in the Root ZX and i-ROOT groups, respectively. Conclusions: In this study, the Apex mark was the more consistent mark. Therefore, it is recommended to subtract 0.5 mm, which is the average length between the apex and apical constriction, from the root canal length at the Apex mark to obtain the working length clinically.
Jin, Kyong-Suk;Park, Jung Ae;Lee, Ji Young;Kang, Ji Sook;Kwon, Hyun Ju;Kim, Byung Woo
Microbiology and Biotechnology Letters
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v.42
no.2
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pp.170-176
/
2014
In this study, the anti-oxidative and anti-inflammatory activities of Euptelea pleiosperma ethanol extract (EPEE) were evaluated using in vitro assays and cell culture model systems. EPEE possessed a more potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl than the ascorbic acid used as a positive control. EPEE effectively suppressed lipopolysaccharide (LPS), in addition to hydrogen peroxide induced reactive oxygen species on RAW 264.7 cells. Furthermore, EPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1) and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), dose and time dependently. The modulation of HO-1 and Nrf2 expression might be regulated by mitogen-activated protein kinases and phosphatidyl inositol 3 kinase/Akt as their upstream signaling pathways. On the other hand, EPEE inhibited LPS induced nitric oxide (NO) formation without cytotoxicity. Suppression of NO formation was the result of the down regulation of inducible NO synthase (iNOS) by EPEE. Suppression of NO and iNOS by EPEE may be modulated by their upstream transcription factor, nuclear factor ${\kappa}B$, and AP-1 pathways. Taken together, these results provide important new insights into E. pleiosperma, namely that it possesses anti-oxidative and anti-inflammatory activities, indicating that it could be utilized as a promising material in the field of nutraceuticals.
This study deals with forest soil characteristics and their effects on the trafficability of logging vehicles. The study area is the national experimental forest located in Kwangnung. This site has 20m length and is equally divided by 5 surveying ranges with 4m width, on which a tractor(FIATAGRI) attached with logging boogie can drive in 4 driving types, namely 1time-return unload, 1time-return with load of 780-790kg weight of 3 logs, 5 and 10times-return with same load. After one driving type on all surveying ranges, the soil hardness is surveyed 5 times with 3 several type tools, SHM-1 type, lang penetrometer(L-PNTM), and clegg impact soil tester(CIST). A disturbed degree of cover vegetation and sliding conditions of vehicle are also observed. As results, the soil type of the test site was SC by USCS and dry brown forest soil. The cover vegetation is gotten trambled under driving after 3-5 times-return, shrubs leaves are fully fallen and their bark are peeled, and after 10 times-return the cover vegetations were nearly disappeared. The test vehicle has neither slided nor was overthrown. The wheel tracks in the 1-3 ranges, of which unit weight(gd, gt) is high and soil moisture content(MC) is low, were only 1-2cm deep, but those in the 4-5 ranges, of which the gd, gt is low and the MC is high, were 5-7cm deep. In the soil hardness test, which was established in 5 test ranges by types of driving, the more driving times, the higher the hardness. The soil hardness surveyed by L-PNTM has changed slowly and that surveyed by SHM-1 type has risen sharply. In the ranges with higher specific gravity(Gs), higher unit weight, lower MC and higher liquid limit(LL) and plasticity index(PI) was the soil hardness high and the trafficability was good. In the ranges with opposite conditions, also in the ranges of the lower soil hardness, the trafficability must be not good, because the wheel track may be deep. The results from CIST attached with 4kg hammer was not better than expected. So it is recommended to use CIST with 2.5kg or 0.5kg hammer.
Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.
Jeon, Hye Lyun;Yi, Jung-Sun;Kim, Tae Sung;Oh, Youkyung;Lee, Hye Jeong;Lee, Minseong;Bang, Jin Seok;Ko, Kinarm;Ahn, Il Young;Ko, Kyungyuk;Kim, Joohwan;Park, Hye-Kyung;Lee, Jong Kwon;Sohn, Soo Jung
Toxicological Research
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v.33
no.2
/
pp.107-118
/
2017
Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.
Kim, Kyung-Ah;Min, Uoo-Gyung;Lim, Jae-Woo;Jun, Nu-Lee;Won, Hye-Sung;Kim, Chung-Hoon;Kim, Ellen Ai-Rhan;Lee, Pil-Ryang;Lee, In-Sik;Kim, Ki-Soo;Kim, Ahm;Pi, Soo-Young
Clinical and Experimental Pediatrics
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v.46
no.3
/
pp.224-229
/
2003
Purpose : To examine various neonatal outcomes and perinatal factors resulting from assisted reproduction compared to that of spontaneous conception. Methods : This is a retrospective study. The control cases were all twins of spontaneous conception born between periods from January 1995 to June 2000. The study cases were identified from twins conceived by assisted reproduction in the same time peried. A total of 460 sets of twins consisted of 250 twins of spontaneous conception and 156 twins of assisted reproduction were studied. The primary outcomes were neonatal morbidity and mortality and the secondary outcomes were perinatal factors including number, length and cost of hospitalization for the delivery. Results : No differences were seen in various neonatal factors including gestational age, birth weight and incidences of respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, hyperbilirubinemia, sepsis, intraventricular hemorrhage and the length of hospitalizations. Lower one minute and five minute Apgar scores and frequently encountered electrolyte abnormalities were observed in neonates of assisted reproduction. In general, the second twin of assisted reproduction had increased incidences of respiratory distress syndrome, sepsis and necrotizing enterocolitis than the first twin. Increased frequencies of preterm labor, hospitalization and elective cesarean section were seen among mothers who underwent artifical conception. However, overall hospital costs in terms of mothers hospitalization for the delivery and neonates hospitalization did not show differences. Conclusion : Assisted reproduction twins had similar neonatal morbidities, mortalities and perinatal morbidities compared to those born by spontaneous conception.
Hepatocytes of Anguilla japonica have been prepared using a collagenase perfusion technique. The isolated cells attached efficiently to fibronectin-coated culture dishes and subsequently formed monolayers in serum-free medium. These cultures maintained in appropriate medium at least for 10 days with minimal cell loss. The effects of estradiol and pituitary hormones on vitellogenin (Vg) synthesis were examined in primary hepatocyte culture of the immature eels. In fish, as in other oviparous vertebrates, estrogen is a major inducer of Vg synthesis. However, $estradiol-17\beta(E_2)$ alone was insufficient to induce Vg synthesis in cultures of eel hepatocytes. Combination of $E_2$ with growth hormone (GH) and/or prolactin (PRL) markedly stimulated Vg synthesis. Even in cultures exposed to $E_2$ or precultured without hormones for 8 days, $E_2$ alone could not fully induce Vg synthesis. The synthesis of Vg was dramatically increased when hepatocytes were cultured in medium supplemented with $E_{2}+GH+PRL$ for 6 days. At this point, even though GH and/or PRL were eliminated from the medium, Vg synthesis was not influenced by these factors during culture of further 3 days. These results indicate that pituitary hormones, in particular GH and PRL, play important roles in the regulation of Vg synthesis in primary cultures of eel hepatocytes.
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