In the present study, we examined the effects of tamoxifen and LY117018 on various parameters for the estrogenic actions in order to understand the mechanism by which tamoxifen and LY117018 act on the uterine cells in 21-23 day old immature rats. Tamoxifen and LY117018 stimulated uterine weight and uterine contents of DNA, protein, and peroxidase activity in the absence of estradiol while inhibited above parameters in the presence of estradiol. Both cytosolic and nuclear progesterone receptors were increased by the treatment of tamoxifen and LY117018 as well as estradiol, but estradiol-induced increase in the progesterone receptors were reduced by the treatment of antiestrogens. These effects were enhanced by the multiple injections of antiestrogens. It seemed that tamoxifen was more agonistic than LY117018 but less antagonistic than LY117018, judged by their effects on various parameters for the estrogenic action. The affinities of estradiol, tamoxifen, and LY117018 for the estrogen receptor were $0.17{\pm}0.01nM(100%)$, $1.10{\pm}0.01nM(6.3%)$, and $0.23{\pm}0.01nM(77%)$, respectively. Furthermore, LY117018 was the competitive ligand for the estrogen receptor in dose-related manner but tamoxifen was not. Following estradiol treatment, nuclear estrogen receptor was sharply increased by 1 h, reaching the maximum by 16 h, while tamoxifen and LY117018 slightly increased nuclear estrogen receptor by 1 h and then decreased thereafter. It is therefore concluded that LY117018 is a competitive antagonist for the estrogen receptor with less estrogenic activity, compared to tamoxifen with low affinity to the estrogen receptor, and tamoxifen may act through other binding site than the estrogen receptor.
The primary objective of this study was to examine the toxic effects of PCP on activated sludge and to analyze its metabolic responses while treating wastewater containing pentachlorophenol (PCP) in a sequencing batch reactor (SBR) system operating under different control strategies. This study was conducted in two phases 1 and 2 (8-hr and 12-hr cycles). Each phase was operated with two control strategies I and II. Strategy I (reactor 1) involved rapid addition (5 minutes to complete) of substrate to the reactor with continuous mixing but no aeration for 2 hours. Strategy ll (reactor 2) involved adding the feed continuously during the first 2 hours of the cycle when the system was mixed but not aerated. During both phases each reactor was operated at a sludge age of 15 days. The synthetic wastewater was used as a feed. The COD of the feed solution was about 380 mg/l. After the reference response for both reactors was established, the steady state response of each system was established for PCP feed concentrations of 0.1 mg/l, 1.0 mg/l, and 5.0 mg/l in SBR systems operating on both 8-hr and 12-hr cycles. Soluble COD removal was not inhibited at any feed PCP concentrations used. At 5.0 mg/l fined PCP concentration and in SBR systems operating on phase 2, the concentrations of MLVSS were decreased; selective pressure on the mixed biomass might be increased, narrowing the range of possible ecological responses; the settleability of activated sludge was poor; the SOURS were increased, showing that the systems were shocked. Nitrification was made to some extent at all concentrations of feed PCP in SBR systems operating on phase 2 whereas in SBR systems operating on phase 1 little nitrification was observed. Then, nitrification will be delayed as much as soluble COD removal is retarded due to PCP inhibition effects. Enhanced biological phosphorus removal occurring in the system operating with control strategy I during phase 1 of this work and in the presence of low concentrations of PCP was unreliable and might cease at anytime, whereas enhanced biological phosphorus removal occurring in the system operating with either control strategy I or II during phase 2 of this work and in the Presence of feed PCP concentrations up to 1.0 mg/l was reliable. When, however, such processes were exposed to 5.0 mg/l PCP dose, enhanced phosphorus removal ceased and never returned.
Journal of the Korean Society of Food Science and Nutrition
/
v.40
no.2
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pp.149-155
/
2011
The objective of this study was to evaluate the antioxidant and antigenotoxic activities of sansuyu fruit (Corni fructus, CF) at temperatures of $25^{\circ}C$, $50^{\circ}C$, and $90^{\circ}C$ using a water extraction method. Total phenolic content (TPC), DPPH radical-scavenging activity (RSA), and superoxide dismutase (SOD)-like activity, and ORAC (Oxygen radical absorbance capacity) values were determined. Also the antigenotoxicity of CF was determined by measuring inhibitory effects of $H_2O_2$ induced DNA damage in human leukocytes using the comet assay. The TPC in the CF extracts was 4.2, 4.6, and 5.5 g/100 g GAE in $25^{\circ}C$, $50^{\circ}C$, and $90^{\circ}C$, respectively. The DPPH RSA of the CF extracts increased in a dose-dependent manner over the range of $50\sim1000\;{\mu}g$/mL in all temperatures and the $SC_{50}$ of DPPH RSA of the CF extracts were not significantly different at different extraction temperatures. The $SC_{50}$ of SOD-like was the highest in CF extracted at $25^{\circ}C$ (1.1 mg/mL) followed by $90^{\circ}C$ (1.2 mg/mL) and $50^{\circ}C$ (1.3 mg/mL). The ORAC values of the CF extracts were not significantly different in low concentration ($10\;{\mu}M$/mL) and was in order of $25^{\circ}C$ ($5.7\;{\mu}M$ TE)< $90^{\circ}C$ ($6.2\;{\mu}M$ TE)< $50^{\circ}C$ ($8.5\;{\mu}M$ TE) in high concentration ($50\;{\mu}M$/mL). $200\;{\mu}M$$H_2O_2$ induced DNA damages in human leukocytes were significantly reduced by the pretreatment with the CF extracts. These results suggest that sansuyu fruit (Corni fructus) can be used as a natural source for antioxidant activities and as antigenotoxic agents regardless of the water extraction temperature.
Ryu, Ji Hyeon;Kim, Eun-Jin;Xie, Chengliang;Nyiramana, Marie Merci;Siregar, Adrian S.;Park, Si-Hyang;Cho, Soo Buem;Song, Dae Hyun;Kim, Nam-Gil;Choi, Yeung Joon;Kang, Sang Soo;Kang, Dawon
Journal of the Korean Society of Food Science and Nutrition
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v.46
no.6
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pp.659-670
/
2017
Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS ($1{\mu}g/kg$) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\alpha}$ expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.
Park, Kyung-Bae;Kim, Young-Mi;Kim, Kyung-Hwa;Shin, Byung-Chul;Park, Woong-Woo;Han, Kwang-Hee;Chung, Young-Ju;Choi, Sang-Mu;Lee, Jong-Doo
The Korean Journal of Nuclear Medicine
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v.34
no.1
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pp.62-73
/
2000
Purpose: Esophageal cancer patients have a difficulty in the intake of meals through the blocked esophageal lumen, which is caused by an ingrowth of cancer cells and largely influences on the prognosis. It is reported that esophageal cancer has a very low survival rate due to the lack of nourishment and immunity as the result of this. In this study a new radioactive stent, which prevents tumor ingrowth and restenosis by additional radiation treatment, has been developed. Materials and Methods: Using ${\ulcorner}HANARO{\lrcorner}$ research reactor, the radioactive stent assembly ($^{166}Ho$-SA) was prepared by covering the metallic stent with a radioactive sleeve by means of a post-irradiation and pre-irradiation methods. Results: Scanning electron microscopy and autoradiography exhibited that the distribution of $^{165/166}Ho\;(NO_3)$ compounds in polyurethane matrix was homogeneous. A geometrical model of the esophagus considering its structural properties, was developed for the computer simulation of energy deposition to the esophageal wall. The dose distributions of $^{166}Ho$-stent were calculated by means of the EGS4 code system. The sources are considered to be distributed uniformly on the surface in the form of a cylinder with a diameter of 20 mm and length of 40 mm. As an animal experiment, when radioactive stent developed in this study was inserted into the esophagus of a Mongrel dog, tissue destruction and widening of the esophageal lumen were observed. Conclusion: We have developed a new radioactive stent comprising of a radioactive tubular sleeve covering the metallic stent, which emits homogeneous radiation. If it is inserted into the blocked or narrowed lumen, it can lead to local destruction of the tumor due to irradiation effect with dilatation resulting from self-expansion of the metallic property. Accordingly, it is expected that restenosis esophageal lumen by the continuous ingrowth and infiltration of cancer after insertion of our radioactive stent will be decreased remarkably.
Gonad and blood samples were taken from the cultured female Korean sea bass, Lateolabrax japonicus from October to February between 1997 and 1999. Gonadosomatic index began to increase in November and reached the highest value in December (12.8$\pm$1.5) and January (14.8$\pm$3.5), and then decreased sharply in February (2.6$\pm$1.5, p<0.05). The ovarian oocytes developed to tertiary yolk stage and reached fully-Brown stage in December and January, and then underwent atresia without maturation and ovulation in February. The plasma estradio3-17 $\beta$ level increased from November, and reached the highest value in December (1,152.3$\pm$107.2 pg/ml) and January (1,315.4$\pm$99.5 pg/ml), after then decreased in February (P<0.05). The concentration of plasma 17 $\alpha$ ,20 $\beta$-dihydroxy-4-pregnen-3-one was not significantly changed at low levels (86.6$\pm$6.5∼93.8$\pm$2.8 pg/ml) during the experimental period (P<0.05). All the fish with fully-grown oocytes in the ovary were matured and ovulated by HCG injection. The number of floating eggs were 325,000$\pm$26,000 at HCG 1,000 luhg and 195,000$\pm$35,000 at 2,000 lUikg. There was no difference in fertilization rate and hatching rate of the eggs (P<0.05). Considering these results, we could infer that the ovarian oocyte of the cultured Korean sea bass were not matured and ovulated because of the lack of gonadotropin surge. Moreover, HCG injection could induce oocyte maturation and ovulation in the cultured fish, and the effective dose was 1,000 IU/kg.
Oh Yoon Kyeong;Ha Chul Soo;Park Hee Chul;Lee Seung Il;Ryu So Yeon;Kee Keun Hong;Jeon Ho Jong
Radiation Oncology Journal
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v.20
no.1
/
pp.34-40
/
2002
Purpose : This study was undertaken to retrospectively evaluate white blood ceil kinetics, especially lymphocyte depression after different treatments, and to find the correlation between immunosuppression and large blood volume and dynamic blood flow within the mediastinal radiotherapy (RT) field in lung cancer. Materials and Methods : Thirty-four patients with lung cancer were retrospectively evaluated; 10 patients had only radiotherapy (RT group), 8 had chemotherapy (CT group) and 16 fad chemotherapy and radio-therapy (RT/CT group). The mean follow-up periods of the RT-including groups (RT group and RT/CT group) and the RT-excluding group (CT group) were 6 and 8 months, respectively. Complete blood cell counts including lymphocyte percentage $(\%)$ were checked weekly during RT but less frequently during CT and after RT and after RT. Results : Changes in total white blood cell counts were not significantly different among the three groups. The lymphocyte count and lymphocyte $\%$ were much lower in the RT-including groups than in the RT-excluding group. The difference between pre-treatment and final lymphocyte count and the difference between pre-treatment and final lymphocyte $\%$ were significant (p=0.044 and p=0.037) between the RT-including groups and the RT-excluding group. Conclusion : lymphopenia was more marked after treatment containing RT than CT only. Lymphopenia may be one cause of a compromised immune system after mediastinal irradiation in lung cancer. We suggest cautiously that previous studies showing evidence of lymphocyte apoptosis after low-dose irradiation and large blood volume and dynamic blood flow within the RT fields could be somewhat related to lymphopenia after mediastinal irradiation.
Purpose: We investigated whether a relationship exists between tumor control dose 50 ($TCD_{50}$) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between $TCD_{50}$, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used In this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were $8{\sim}12$ weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for $TCD_{50}$, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of $p53,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-X_L,\;Bcl-X_S$, and p34. Correlation analysis was peformed whether the level of RIA were correlated with $TCD_{50}$ or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with $TCD_{50}$, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with $TCD_{50}$ (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of $p21^{WAF1/CIP1}$ and 34 showed a significant correlation either with $TCD_{50}$ (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890 p=0.043). The tumors with high constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 can be used as biological markers which predict the radiosensitivity.
[ $\underline{Purpose}$ ]: We performed a retrospective non-randomized clinical study of locally advanced rectal cancer, to evaluate the anal sphincter preservation rates, down staging rates and survival rates of preoperative chemoradiotherapy. $\underline{Materials\;and\;Methods}$: From January 2002 to December 2005, patients with pathologically confirmed rectal cancer with clinical stage T2 or higher, or patients with lymph node metastasis were enrolled in this study. A preoperative staging work-up was conducted in 36 patients. All patients were treated with preoperative chemoradiotherapy, and curative resection was performed for 26 patients at Hallym University Sacred Heart Hospital. Radiotherapy treatment planning was conducted with the use of planning CT for all patients. A total dose of $45.0{\sim}52.2\;Gy$ conventionally fractionated three-dimensional radiotherapy was delivered to the whole pelvis. Chemotherapy was given at the first and fifth week of radiation therapy with continuous infusion i.v. 5-FU (Fluorouracil) and LV (Leucovorine). Surgical resection was performed 2 to 4 weeks after the completion of the chemoradiotherapy regimen. $\underline{Results}$: The complete resection rate with negative resection margin was 100% (26/26). However, a pathologically complete response was not seen after curative resection. Surgery was done by LAR (low anterior resection) in 23 patients and APR (abdomino-perineal resection) in 3 patients. The sphincter preservation rate was 88.5% (23/26), down staging of the tumor occurred in 12 patients (46.2%) and down-sizing of the tumor occurred in 19 patients (73%). Local recurrence after surgical resection developed in 1 patient, and distant metastasis developed in 3 patients. The local recurrence free survival rate, distant metastasis free survival rate, and progression free survival rate were 96.7%, 87% and 83.1%, respectively. Treatment related toxicity was minimal except for one grade 3, one grade 4 anemia, one grade 3 leukopenia, and one grade 3 ileus. $\underline{Conclusion}$: Preoperative concurrent chmoradiotherapy for locally advanced rectal cancer seems to have some potential benefits: high sphincter preservation and down staging. Treatment related toxicity was minimal and a high compliance with treatment was seen in this study. Further long-term follow-up with a larger group of patients is required.
Eugenol (4-allyl-2-methoxyphenol) is a main component of essential oils obtained from various spices. Recent reports have shown that eugenol induces growth inhibition and apoptosis of malignant tumor cells. In this study, the stimulatory effect of eugenol on cell differentiation was investigated in HL-60 promyelocytic leukemia cells. When HL-60 cells were treated in combination with 150 ${\mu}M$ of eugenol and 3 nM of $1{\alpha},25-dihydroxyvitamin$$D_{3}$, cell growth was slower than that of cells treated with eugenol or $1{\alpha},25-dihydroxyvitamin$$D_{3}$ alone. Eugenol enhanced low dose of $1{\alpha,25-dihydroxyvitamin }$$D_{3}-induced$ a $G_{0}/G_{1}$ phase arrest in cell cycle. Consistent with this, combined treatment of eugenol and $1{\alpha},25-dihydroxyvitamin$$D_{3}$ cooperatively increased p27 level and decreased cyclin A, cdk 2 and cdk 4 levels, which are cell cycle regulators related to $G_{0}/G_{1}$ arrest. According to flow cytometric analysis, the expression of CD14 (monocytic differentiation marker) was more increased in the cells co-treated with eugenol and $1{\alpha},25-dihydroxyvitamin$$D_{3}$. These results indicate that eugenol potentiates cell differentiation mediated by $1{\alpha},25-dihydroxyvitamin$$D_{3}$ of suboptimal concentration. The differentiation-inducing property of eugenol maybe contributes to chemopreventive activity of cancer.
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