Kim, Yeon-Sil;Roh, Kwang-Won;Chae, Soo-Min;Mun, Seong-Kwon;Yoon, Sei-Chul;Jang, Hong-Seok;Chung, Su-Mi
Radiation Oncology Journal
/
v.25
no.4
/
pp.233-241
/
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.
Seo, Ji-Young;Yoon, In-Suk;Shin, Choong-Ho;Yang, Sei-Won
Clinical and Experimental Pediatrics
/
v.49
no.3
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pp.305-311
/
2006
Purpose : GnRH analogues(GnRHa) are used to treat central precocious puberty(CPP). However, in some patients, the GV decrease is so remarkable that it impairs predicted adult height(PAH); and there fore, the addition of growth hormone(GH) is suggested. We analysed the growth changes during two years and final adult height(FAH) in girls with idiopathic CPP treated with combined therapy, compared with those of girls treated with GnRHa alone. Methods : For the analysis, we classified the patients, who was treated for longer than two years, into three groups depending on the initial PAH and combination of GH; PAH_L, treated with GnRHa and PAH less than midparental height(MPH) - 5 cm. PAH_H, treated with GnRHa and PAH greater than MPH - 5 cm. GnRHa+GH, combined GH treatment, regardless of PAH before treatment. We analysed the GV and PAH change during the first two years and FAH. Results : In PAH_L, the PAH(SDS) at first year of therapy was significantly increased to $153.5{\pm}6.5cm(-1.4{\pm}1.3)$ from $149.7{\pm}6.4cm(-2.1{\pm}1.3)$ before treatment(P=0.004). In PAH_H, there was no significant increase in PAH during the two years of treatment. During the first year of combination of GH and GnRHa, GV and PAH increased significantly. We observed significant increases in FAH, comparing to the initial PAH in the PAH_L and GnRHa+GH groups. The height gains(FAH - initial PAH) were significantly higher in the PAH_L and GnRHa+GH groups than that in the PAH_H group. Conclusion : This study suggests the FAH and height gains are improved in patients, whose predicted adult height before treatment was shorter than those with higher predicted adult height, with the treatment of GnRHa alone or in combination with GH. GH could not improve the final adult height, but compensated the growth in patients whose growth velocity was decelerated by GnRHa alone.
Kim, Jae Hyun;Lee, Sung Soo;Hong, Su Young;Chung, Hye Rim;Shin, Choong Ho;Yang, Sei Won
Clinical and Experimental Pediatrics
/
v.48
no.2
/
pp.191-196
/
2005
Purpose : Short stature is one of the characteristic features of Turner syndrome. We investigated the factors affecting final adult height(FAH) in patients with Turner syndrome. Methods : The study group was comprised of 60 patients who were diagnosed with Turner syndrome by chromosomal study and clinical phenotypes and attained FAH. Data were obtained from retrospective review of the medical records. We analyzed the factors influencing FAH in growth hormone(GH) treated and GH untreated groups. Results : Sixty patients were enrolled; 48 patients received GH treatment, and 12 patients did not. Mean duration of GH treatment was 35.8 months(range 4 to 120 months), and mean dosage of GH was $0.8{\pm}0.2IU/kg/wk$ in GH treated group. Mean growth velocity was $5.6{\pm}2.0cm/yr$, which was significantly higher than that during pretreatment period. In the GH treated group, mean chronological age, bone age, mean height, and height standard deviation(SD) score at GH treatment were $12.2{\pm}2.7yr$$10.3{\pm}2.5yr$$127.5{\pm}10.1cm$ and $-3.1{\pm}1.1$, respectively. In the GH treated group, the mean FAH and SD score of FAH were $146.9{\pm}5.8cm$ and $-2.7{\pm}1.2$, respectively, which showed significant differences compared with those of the GH untreated group. Analyzing the factors affecting FAH in GH-treated patients, only the SD score of height at the time of treatment was significantly related to FAH. Conclusion : GH treatment leads to an increment in FAH in patients with Turner syndrome. Average FAH gain was as much as 5.8 cm. SD score of height at the time of GH treatment was the only factor influencing FAH.
Kim, Sang Woo;Yoon, Sei Hyung;Kim, Jae-Hwan;Ko, Yeoung-Gyu;Kim, Dong Hoon;Kang, Geun Ho;Kim, Young-Sin;Lee, Sang Moo;Suh, Sang Won
Journal of The Korean Society of Grassland and Forage Science
/
v.32
no.4
/
pp.429-436
/
2012
This study was conducted to examine the effect of feeding levels of concentrate feed on growth performance, meat quality and economic evaluation of Korean black goats. The 40 male Korean native goat were divided into four treatment groups T1 (1.5%), T2 (2.0%), T3 (2.5% feeding of concentrate feed body weight per day) and T4 (ab libitum) with ab libitum rice straw. Rice straw intake decrease as against feeding levels, however average daily gains were 22, 50, 69 and 94 g/day in T1, T2, T3 and T4 groups respectively levels (p<0.05). Dressing percentage were 41.77, 42.78, 46.12 and 49.78% in each group (p<0.05), also fat percentage were a significant increase according to feeding levels. In economic efficacy, T4 was higher than other treatment groups. In conclusion, both rice straw and concentrate feed ab libitum are good for feeding and management system on Korean black goats.
Kim, Hak-Ryul;Jung, Jong-Hoon;Kim, Hwi-Jung;Yang, Sei-Hoon;Jeong, Eun-Taik
Tuberculosis and Respiratory Diseases
/
v.57
no.5
/
pp.443-448
/
2004
Background : Small-cell carcinomas of lung have a tendency for rapid growth and early wide metastasis. Despite the high response rates of combination chemotherapy alone or with radiotherapy, the overall long-term survival rate is very disappointing. According to autopsy findings, the common cause of failure is local recurrence in the primary cancer site. Therefore, surgical resection with combined chemotherapy has recently been attempted for very early stage small-cell carcinomas of the lung. Methods : 10 patients (TNM I & II: 5 cases each) undergoing surgical resection for small-cell carcinomas of the lung were treated with adjuvant chemotherapy in an attempt to prolong survival. Of these, 9 patients received chemotherapy, and a retrospective study for survival undertaken (Kaplan-Meier analysis). Results : The median survival time was 26 months, and the 2- and 5-year survival rates were 68.6 and 46.7%, respectively. If the 1 patient not having undergone chemotherapy was excluded, the 2-, 5-year survival rates were 76.2 and 50.8%, respectively? No difference in the survival rate was seen between patients with TNM stages I and II. Conclusion : Adjuvant chemotherapy after surgical resection results in prolonged survival for patients with TNM stages I and II small-cell carcinomas of the lung.
Background : Non-steroidal anti-inflammatory drugs (NSAID) are useful in chemoprevention of colorectal cancers. Continuous NSAID administation causes 40% to 50% reduction in relative risk for colorectal cancer. Sulindac possesses an antiproliferative effect and induces apoptosis and tumor regression on colon cancer and other types of cancers. We intended to analyze the effects of sulindac in three non-small cell lung cancer cell lines. Materials and Methods : The human lung cancer cell lines, A549, NCI-H157 and NCI-H460 were used for this study. Viability was tested by MTT assay, and cell death rate was measured by lactate dehydrogenase(LDH) release. Apoptosis was estimated by flow cytometric analysis and nuclear staining. Results: Sulindac was able to decrease the viability of non-small cell lung cancer cells in a dose- and time- dependent manner. In a parallel effect of sulindac on cell death rate, LDH release was increased in sulindac-treated lung cancer cells. Sulindac significantly increased apoptosis characterized by an increase of $sub-G_0/G_1$ fraction and morphological change of nuclei. The rate of apoptotic cells after sulindac treatment in lung cancer cells increased in a time- and dose- dependent manner in flow cytometric analysis. Apoptotic cells were defined as nuclear shrinkage, chromatin condensation and nuclear fragmentation of cells. Conclusion : Sulindac decreases viability and induces the apoptosis of lung cancer cells. Further studies will be needed to elucidate the potential mechanism of sulindac-induced apoptosis in lung cancer cells.
A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.
Journal of The Korean Society of Grassland and Forage Science
/
v.28
no.1
/
pp.13-18
/
2008
This experiment was conducted to compare the agronomic characteristics, flowering condition and productivity of introduced annual legumes at paddy field of Seonghwan(Cheonan, Chungnam, Korea) from September 2006 to May 2007. Annual legumes used in this study were hairy vetch(Vicia villsa, Rosa), crimson clover(Trifolium incarnatum, Contea), berseem clover(Trifolium alexandrinum, Alexandria), persian clover(Trifolium resupinatum, Prolific), balansa clover(Trifolium michelianum, Paradona), sweet clover(Melilotus officinalis, Yellow) and forage pea(Pisum sativum, Austrian). Emergency rate after seeding were 90% or more in crimson clover, hairy vetch, forage pea and berseem clover. Wintering of hairy vetch and crimson clover were excellent as 98% and 95%, respectively. Flowering rate of harvesting date(May 10) was 100% in crimson clover, 98% in balansa clover, 5% in persian clover and others were not flowering. Fresh and dry matter yield of crimson clover were highest as 72,556 kg/ha and 16,062 kg/ha, respectively. Crude protein yield of hairy vetch was highest as 2,929 kg/ha but not significant with crimson clover(2,169 kg/ha). TDN yield of crimson clover was highest as 9,007 kg/ha but not significant with hairy vetch(7,366 kg/ha). According to the results from this study, it is suggested that crimson clover would be recommendable for autumn-sowing annual legume at paddy field of Central Provinces.
Results as follows are obtained from the pot experiment to examine effect of application of organic substances on inhibition of occurrence of root rot of red pepper. 1. As for effects of applicating organic materials on inhibition of red pepper root rot, it is more effective to apply in autumn than to apply in summer, when the temperature is high. In addition, organic substance which is not decomposed completely such as rice straw is more effective than matured compost types. As for effects of applicating organic substances on composition of soil microorganisms, increase of fungi and bacteria in view of numbers is remarkable, especially in case of applying rice straw. 2. From the examination of Phytophthora capsici in soil at the 1st cultivation period in autumn, no P. capsici can be isolated in early stage of growth of red pepper in nontreated soil and in soil applied compost. However, as the time goes on, P. capsici are detected. While in early stage of cultivation, P. capsici are detected in soil applied with rice straw, P. capsici are not isolated after middle stage of cultivation. 3. It is recognized that there are many differences according to the types of organic materials applied in the result of identification of fungi in each treatment. And, proportion of antagonistic fungi to total fungi in soil applied rice straw is proved to be significantly higher compared to other treatments.
Background : Cyclooxygenase is the main target enzyme for the nonsteroidal anti inflammatory drugs (NSAIDs) that have been shown to suppress carcinogenesis in both experimental models and epidemiological studies. COX-2 plays an important role in solid tumor growth, invasiveness and angiogenesis, through, in part, the synthesis of prostaglandins, such as prostaglandin E2 (PGE2). In this study, the prognostic significance of an increase in COX-2 expression in lung cancer samples was evaluated. Material and Methods : The expression of COX-2, by immunohistochemistry, was studied in paraffin-embedded tumor blocks obtained from 84 patients(male 67, female 17, with a mean age of 63, ranging from 34 to 84 years) who had undergone surgery at Wonkwang University Hospital, between 1997 and 2002. For the evaluation of the relationships between COX-2 expression, and the clinical stage, metastasis to lymph nodes and survival, those cases showing the respective antigen expression in >10% of the tumor cells were considered positive. Result : Of the 84 patients, 61 (73%) exhibited more than 10% COX-2 immunoreactivities in the tumor and normal cells, whereas the remaining 23 showed no increase in the expression of COX-2. There was no significant relationship between the increased expression of COX-2 and the disease stage(p=0.1002) or cell type(p=0.152). The median survival was longer for the patients with a negative, compared to positive, COX-2 expression(36 compared to 24 months, p<0.05). The two year-survival rate was also higher in the patients with a negative COX-2 expression (78%) than those with a positive expression (47%, Kaplan-Meier, Log Rank, p < 0.05). Conclusion : The median survival was longer in the patients with a negative, compared to positive, COX-2 expression was longer than those with positive COX-2, having undergone complete resection due to primary non-small cell lung cancer.
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